Peptide nanostructures encapsulating a foreign material and method of manufacturing same

ABSTRACT

A composition comprising a material at least partially enclosed by a tubular, spherical or planar nanostructure composed of a plurality of peptides, wherein each of the plurality of peptides includes no more than 4 amino acids and whereas at least one of the 4 amino acids is an aromatic amino acid.

RELATED APPLICATIONS

This application is a Divisional of U.S. patent application Ser. No.11/148,266 filed on Jun. 9, 2005, which is a Continuation-In-Part ofPCT/IL2004/000012 filed on Jan. 7, 2004, which claims the benefit ofU.S. Provisional Patent Application Nos. 60/438,331 filed on Jan. 7,2003 and 60/458,378 filed on Mar. 31, 2003.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to peptide nanostructures and morespecifically to peptide nanostructures encapsulating foreign materials.

Nanoscience is the science of small particles of materials and is one ofthe most important research frontiers in modern technology. These smallparticles are of interest from a fundamental point of view since theyenable construction of materials and structures of well-definedproperties. With the ability to precisely control material propertiescome new opportunities for technological and commercial development, andapplications of nanoparticles have been shown or proposed in areas asdiverse as micro- and nanoelectronics, nanofluidics, coatings and paintsand biotechnology.

It is well established that future development of microelectronics,magnetic recording devices and chemical sensors will be achieved byincreasing the packing density of device components. Traditionally,microscopic devices have been formed from larger objects, but as theseproducts get smaller, below the micron level, this process becomesincreasingly difficult. It is therefore appreciated that the oppositeapproach is to be employed, essentially, the building of microscopicdevices from a molecular level up, primarily via objects of nanometricdimensions. Self-assembled nanoparticles, such as nanotubes andnanospheres, allow controlled fabrication of novel nanoscopic materialsand devices. Such nanostructures have found use in areas as diverse asmicro- and nanoelectronics, nanofluidics, coatings and paints andbiotechnology.

In particular, wire-like semiconducting nanostructures have attractedextensive interest over the past decade due to their great potential foraddressing some basic issues about dimensionality and space confinedtransport phenomena as well as related applications. Wire-likesemiconducting nanostructures often have distinctive properties and canbe used as transparent conducting materials and gas sensors. Forexample, fluorine-doped tin oxide films are used in architectural glassapplications because of their low emissivity for thermal infrared heat.Tin-doped indium oxide films can be used for flat panel displays due totheir high electrical conductivity and high optical transparency.

In the field of magnetic recording, wire-like nanostructures can be usedas magnetoresistive read transducers. It has been well known that themagnetoresistive sensors are capable of reading information from thesurface of magnetic recording media at high linear densities. Themagnetoresistive sensors sense magnetic signals by way of the electricalresistance change of magnetoresistive elements that varies as a functionof the strength and orientation of the magnetic flux sensed by read ormagnetoresistive elements. The use of nanoscale elements in such sensorssignificantly increases the capability of retrieving accurateinformation from highly dense magnetic media.

In the field of displays, much effort has been devoted to developedelectrophoretic displays. Such displays use a display medium comprisinga plurality of electrically charged particles suspended in a fluid.Electrodes are provided adjacent the display medium so that the chargedparticles can be moved through the fluid by applying an electric fieldto the medium. In one type of such electrophoretic display, the mediumcomprises a single type of particle having one optical characteristic ina fluid which has a different optical characteristic. In a second typeof such electrophoretic display, the medium contains two different typesof particles differing in at least one optical characteristic and inelectrophoretic mobility.

The most widely used building blocks of nano-materials and nano-devicesare the fullerene carbon nanotubes. Two major forms of carbon nanotubesexist, single-walled nanotubes (SWNT), which can be considered as longwrapped graphene sheets and multi walled nanotubes (MWNT) which can beconsidered as a collection of concentric SWNTs with different diameters.

SWNTs have a typical length to diameter ratio of about 1000 and as suchare typically considered nearly one-dimensional. These nanotubes consistof two separate regions with different physical and chemical properties.A first such region is the side wall of the tube and a second region isthe end cap of the tube. The end cap structure is similar to a derivedfrom smaller fullerene, such as C₆₀.

Since nanotubes have relatively straight and narrow channels in theircores, it was initially suggested that these cavities may be filled withforeign materials to fabricate one dimensional nanowires. Earlycalculations suggested that strong capillary forces exist in nanotubes,which are sufficient to hold gases and fluids inside them [Pederson(1992) Phys. Rev. Lett. 69:2689]. The first experimental proof wasprovided by Pederson and co-workers, who showed filling andsolidification of molten leaf inside nanotubes [Pederson (1992) Phys.Rev. Lett. 69:415]. Various other examples, concerning the filling ofnanotubes with metallic and ceramic materials exist in the literature[Ajayan (1993) Nature 361:392; Tsang (1994) Nature 372:416; Dujardin(1994) 265:1850].

Despite high applicability, the process of filling carbon nanotubes isdifficult and inefficient. Most commonly produced carbon nanotubes, arecapped at least one end of the tube and no method for efficientlyopening and filling the carbon nanotubes with foreign material is knownto date. For example, nanotube ends can be opened by post oxidationtreatment in an oxygen atmosphere at high temperature. The majordrawback of such a procedure is that the tube ends become filled withcarbonaceous debris. As a consequent, filling the open-ended tubes afterpost oxidation with other material has proven difficult. Another problemwith carbon nanotubes synthesized in inert gas arcs is the formation ofhighly defective tubes containing amorphous carbon deposits on both theinside surface and outside surface of the tubes and the presence ofdiscontinuous graphite sheets. Furthermore, since carbon nanotubes arecurved, wetting may prove difficult. Finally, since the internal cavityof SWNTs is very small, filling can be done only for a very limitednumber of materials.

Recently, peptide building blocks have been shown to form nanotubes.Peptide nanotubes are of a special interest since they are biocompatibleand can be easily chemically modified.

Peptide-based nanotubular structures have been made through stacking ofcyclic D-, L-peptide subunits. These peptides self-assemble throughhydrogen-bonding interactions into nanotubules, which in-turnself-assemble into ordered parallel arrays of nanotubes [Ghadiri, M. R.et al., Nature 366, 324-327 (1993); Ghadiri, M. R. et al., Nature 369,301-304 (1994); Bong, D. T. et al., Angew. Chem. Int. Ed. 40, 988-1011(2001)].

More recently, surfactant-like peptides that undergo spontaneousassembly to form nanotubes with a helical twist have been reported. Themonomers of these surfactant peptides have distinctive polar andnonpolar portions. They are composed of 7-8 residues, approximately 2 nmin length when fully extended, and dimensionally similar tophospholipids found in cell membranes. Although the sequences of thesepeptides are diverse, they share a common chemical property, i.e.; ahydrophobic tail and a hydrophilic head. These peptide nanotubes, likecarbon and lipid nanotubes, also have a very high surface area to weightratio. Molecular modeling of the peptide nanotubes suggests a possiblestructural organization [Vauthey (2002) Proc. Natl. Acad. Sci. USA99:5355; Zhang (2002) Curr. Opin. Chem. Biol. 6:865]. Based onobservation and calculation, it is proposed that the cylindricalsubunits are formed from surfactant peptides that self-assemble intobilayers, where hydrophilic head groups remain exposed to the aqueousmedium. Finally, the tubular arrays undergo self-assembly throughnon-covalent interactions that are widely found in surfactant andmicelle structures and formation processes.

Peptide based bis(N-α-amido-glycyglycine)-1,7-heptane dicarboxylatemolecules were also shown to be assembled into tubular structures[Matsui (2000) J. Phys. Chem. B 104:3383].

However, although at least some of the above-described peptides wereshown to form open-ended nanotubes [Hartgerink (1996) J. Am. Cham. Soc.118:43-50], these are composed of peptide building blocks, which arerelatively long and as such are expensive and difficult to produce, orlimited by heterogeneity of structures that are formed as bundles ornetworks rather than discrete nanoscale structures.

There is thus a widely recognized need for, and it would be highlyadvantageous to have, hollow peptide nanostructures, which are devoid ofthe above limitations.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided acomposition comprising a material at least partially enclosed by atubular, spherical or planar nanostructure composed of a plurality ofpeptides, wherein each of the plurality of peptides includes no morethan 4 amino acids and whereas at least one of the 4 amino acids is anaromatic amino acid.

According to another aspect of the present invention there is provided amethod of encapsulating material in a tubular, spherical or planarnanostructure, the method comprising: (a) providing the tubular orspherical nanostructure composed of a plurality of peptides, whereineach of the plurality of peptides includes no more than 4 amino acidsand whereas at least one of the 4 amino acids is an aromatic amino acid,the tubular or spherical nanostructure having an internal cavity; and(b) introducing the material into the internal cavity of the tubular orspherical nanostructure, thereby encapsulating the material in thetubular or spherical nanostructure.

According to yet another aspect of the present invention there isprovided a method of encapsulating material in a tubular, spherical orplanar nanostructure, the method comprising assembling the tubular orspherical nanostructure composed of a plurality of peptides, whereineach of the plurality of peptides includes no more than 4 amino acidsand whereas at least one of the 4 amino acids is an aromatic amino acidin the presence of the material, there by encapsulating the material onthe tubular or spherical nanostructure.

According to still another aspect of the present invention there isprovided a composition comprising a material at least partially enclosedby a tubular, spherical or planar nanostructure composed of polyaromaticpeptides.

According to an additional aspect of the present invention there isprovided a method of positioning a target molecule at a predeterminedlocation, the method comprising: (a) providing a magnetic nanowirehaving at least one segment associated with a functional group orligand, the functional group or ligand being capable of binding to thetarget molecule; (b) binding the magnetic nanowire to the targetmolecule; and (c) exposing the magnetic nanowire to a magnetic field, soas to position the magnetic nanowire and the target molecule at thepredetermined location; wherein the nanowire is formed of a magneticmaterial at least partially enclosed by a nanostructure composed of aplurality of peptides, each of the plurality of peptides including nomore than 4 amino acids, whereas at least one of the 4 amino acids is anaromatic amino acid.

According to further features in preferred embodiments of the inventiondescribed below, the functional group is selected from the groupconsisting of thiols, disulfides, cyanides, amines, carboxylic acids,phosphonates, siloxanes and hydroxamic acids.

According to still further features in the described preferredembodiments the ligand is selected from the group consisting ofproteins, fibronectin, DNA, RNA, enzymes, ribozymes, hydrophobicmaterials, hydrophillic materials, cells, tissue, microorganisms,bacteria, viruses and chemoattractant.

According to still further features in the described preferredembodiments the method further comprises monitoring the target moleculeusing a light-emitting material at least partially enclosed by thenanostructure.

According to yet an additional aspect of the present invention there isprovided a method of delivering an agent to a subject, the methodcomprising: providing a composition having the agent at least partiallyenclosed by a tubular, spherical or planar nanostructure; andadministrating the nanostructure to the subject; wherein thenanostructure is composed of a plurality of peptides, each of theplurality of peptides including no more than 4 amino acids and whereasat least one of the 4 amino acids is an aromatic amino acid.

According to still further features in the described preferredembodiments the agent is a therapeutic agent.

According to still further features in the described preferredembodiments the therapeutic agent is an anti-cancer drug.

According to still further features in the described preferredembodiments the method further comprises monitoring the agent using alight-emitting material at least partially enclosed by thenanostructure.

According to still an additional aspect of the present invention thereis provided a thermoelectric device, comprising a first heat conductinglayer and a second heat conducting layer, the first and the second heatconducting layers being interposed by a plurality of nanowires, suchthat when current flows through the plurality of nanowires, heat istransferred out of the first heat conducting layer and is dissipatedthrough the second heat conducting layer; wherein each of the pluralityof nanowires is formed of a thermoelectric material at least partiallyenclosed by a nanostructure composed of a plurality of peptides, andwherein each of the plurality of peptides includes no more than 4 aminoacids, such that at least one of the 4 amino acids is an aromatic aminoacid.

According to a further aspect of the present invention there is provideda thermoelectric system having an arrangement of thermoelectric devices,each one of the thermoelectric devices comprising a first heatconducting layer and a second heat conducting layer, the first and thesecond heat conducting layers being interposed by a plurality ofnanowires, such that when current flows through the plurality ofnanowires, heat is transferred out of the first heat conducting layerand is dissipated through the second heat conducting layer; wherein eachof the plurality of nanowires is formed of a thermoelectric material atleast partially enclosed by a nanostructure composed of a plurality ofpeptides, and wherein each of the plurality of peptides includes no morethan 4 amino acids, such that at least one of the 4 amino acids is anaromatic amino acid.

According to yet a further aspect of the present invention there isprovided a thermoelectric device, comprising at least three heatconducting regions and at least one semiconducting region beingconnected to at least one heat conducting region of the at least threeheat conducting regions via at least one nanowire formed of a conductingor thermoelectric material, at least partially enclosed by ananostructure composed of a plurality of peptides, each of the pluralityof peptides including no more than 4 amino acids, whereas at least oneof the 4 amino acids is an aromatic amino acid; the at least three heatconducting regions and the at least one semiconducting region beingarranged in the thermoelectric device such that when current flowstherethrough, heat is transferred out of at least one of the at leastthree heat conducting regions.

According to further features in preferred embodiments of the inventiondescribed below, the at least one semiconducting region is formed of amaterial selected from the group consisting of CdS, CdSe, ZnS and SiO₂.

According to still a further aspect of the present invention there isprovided a method of characterizing a nucleic acid sequence of apolynucleotide, the method comprising: (a) positioning thepolynucleotide in a nanogate defined by two conducting nanowires, eachof the two conducting nanowires being formed of a conducting material atleast partially enclosed by a nanostructure composed of a plurality ofpeptides, each of the plurality of peptides including no more than 4amino acids, wherein at least one of the 4 amino acids is an aromaticamino acid; (b) applying a tunneling voltage to the nanogate so as togenerate electron tunneling between the two conducting nanowires; and(c) measuring at least one parameter characteristic of the nucleic acidsequence of the polynucleotide.

According to further features in preferred embodiments of the inventiondescribed below, the positioning the molecule is by generating anelectric field capable of inducing electrophoresis forces on thepolynucleotide.

According to still a further aspect of the present invention there isprovided an apparatus for characterizing a nucleic acid sequence of apolynucleotide, the apparatus comprising: (a) a nanogate defined by twoconducting nanowires, each of the two conducting nanowires being formedof a conducting material at least partially enclosed by a nanostructurecomposed of a plurality of peptides, each of the plurality of peptidesincluding no more than 4 amino acids, wherein at least one of the 4amino acids is an aromatic amino acid; and (b) a positioning device forpositioning the polynucleotide within the nanogate; the positioningdevice and the nanogate being designed and constructed such that whenthe polynucleotide is positioned within the nanogate and a voltage isapplied thereto, electron tunneling is generated between the twoconducting nanowires, the electron tunneling having at least oneparameter characteristic of the nucleic acid sequence of thepolynucleotide.

According to further features in preferred embodiments of the inventiondescribed below, the positioning the molecule comprises an arrangementof electrodes designed and constructed to generate an electric fieldcapable of inducing electrophoresis forces on the polynucleotide.

According to still further features in the described preferredembodiments the at least one parameter is selected from the groupconsisting of a tunneling current, a tunneling current-voltage curve, atunneling current derivative, a current-slope-voltage curve and adielectric constant.

According to still a further aspect of the present invention there isprovided a display system comprising: (a) a fluid containing a pluralityof nanostructure devices, each being formed of a conducting orsemiconducting material at least partially enclosed by a nanostructurecomposed of a plurality of peptides, each of the plurality of peptidesincluding no more than 4 amino acids, whereas at least one of the 4amino acids is an aromatic amino acid; (b) an electric field generatorcapable of generating an electric field effective in shifting thenanostructure devices between a dispersed state and an aggregated state;wherein a size of the nanostructure devices is selected such that whenthe nanostructure devices are in the dispersed state, the fluid presentsa first optical characteristic, and when the nanostructure devices arein the aggregated state, the fluid presents a second opticalcharacteristic.

According to further features in preferred embodiments of the inventiondescribed below, the first and the second optical characteristicscomprise characteristic wavelength.

According to still further features in the described preferredembodiments the first and the second optical characteristics comprisecharacteristic intensity.

According to still further features in the described preferredembodiments the first and the second optical characteristics comprisecharacteristic wavelength and characteristic intensity.

According to still further features in the described preferredembodiments the nanostructure devices comprises a light-emittingmaterial.

According to still a further aspect of the present invention there isprovided a transistor, comprising a first nanowire and a second nanowireforming a junction with the first nanowire, each of the first nanowireand the second nanowire being formed of a semiconducting material, atleast partially enclosed by a nanostructure composed of a plurality ofpeptides, each of the plurality of peptides including no more than 4amino acids, whereas at least one of the 4 amino acids is an aromaticamino acid; wherein the semiconducting material of the first nanowirehas an n-type doping and the semiconducting material of the secondnanowire has a p-type doping.

According to still a further aspect of the present invention there isprovided a crossbar array, comprising a plurality of junctions eachformed by a pair of crossed nanowires and at least one connectorconnecting the pair of crossed nanowires, the at least one connector andthe pair of crossed nanowires form an electrochemical cell; wherein eachof the crossed nanowires is formed of a conducting or semiconductingmaterial, at least partially enclosed by a nanostructure composed of aplurality of peptides, each of the plurality of peptides including nomore than 4 amino acids, whereas at least one of the 4 amino acids is anaromatic amino acid.

According to further features in preferred embodiments of the inventiondescribed below, the at least one connector forms a quantum statemolecular switch having an electrically adjustable tunnel junctionbetween the two nanowires.

According to still further features in the described preferredembodiments each of the plurality of junctions forms an electronicelement, selected from the group consisting of a resistor, a tunnelingresistor, a diode, a tunneling diode, a resonant tunneling diode and abattery.

According to still a further aspect of the present invention there isprovided a device for detecting a position and/or movement of an object,the device comprising a plurality of non-intersecting nanowires, eachbeing connected to an electronic circuitry, such that when the objectcontacts at least one nanowire of the plurality of non-intersectingnanowires, the at least one nanowire intersects with at least oneadditional nanowire of the plurality of non-intersecting nanowires,thereby allowing the electronic circuitry to generate a signalrepresentative of the position and/or movement of an object; whereineach of the plurality of nanowires is formed of a conducting or magneticmaterial at least partially enclosed by a nanostructure composed of aplurality of peptides, each of the plurality of peptides including nomore than 4 amino acids, whereas at least one of the 4 amino acids is anaromatic amino acid.

According to still a further aspect of the present invention there isprovided an electronic circuit assembly, comprising conductive linesbeing arranged in at least two layers separated therebetween by adielectric layer, wherein conductive lines of at least a pair of layersof the at least two layers are electrically connected therebetween viaat least one nanowire formed of a conducting material at least partiallyenclosed by a nanostructure composed of a plurality of peptides, each ofthe plurality of peptides including no more than 4 amino acids, whereasat least one of the 4 amino acids is an aromatic amino acid.

According to still a further aspect of the present invention there isprovided a memory cell, comprising: a plurality of magnetic nanowireseach formed of a ferromagnetic material at least partially enclosed by ananostructure composed of a plurality of peptides, each of the pluralityof peptides including no more than 4 amino acids, whereas at least oneof the 4 amino acids is an aromatic amino acid; wherein each of theplurality of magnetic nanowires is capable of assuming two magnetizationstates and is connected to two conductive lines defining an address of amagnetic nanowire connected thereto.

According to further features in preferred embodiments of the inventiondescribed below, the memory cell further comprises a membrane throughwhich the plurality of magnetic nanowires extend, wherein the twoconductive lines engage opposite sides of the membrane.

According to still a further aspect of the present invention there isprovided a memory cell, comprising: (a) an electrode; and (b) ananowire, formed of a conducting material, at least partially enclosedby a nanostructure composed of a plurality of peptides, each includingno more than 4 amino acids, wherein at least one of the 4 amino acids isan aromatic amino acid, the nanowire being capable of assuming one of atleast two states; the nanostructure and the electrode being designed andconstructed such that when electrical current flows through theelectrode, the nanostructure transforms from a first state of the atleast to states to a second state of the at least to states.

According to further features in preferred embodiments of the inventiondescribed below, the transformation from the first state to the secondstate comprises a geometrical deflection of the nanowire.

According to still a further aspect of the present invention there isprovided a field emitter device, comprising an electrode and a nanowire,the electrode and the nanowire being designed and constructed such thatwhen an electrical field is formed therebetween, electrons are emittedfrom the nanowire, wherein the nanowire is formed of a conductingmaterial, at least partially enclosed by a nanostructure composed of aplurality of peptides, each including no more than 4 amino acids andwherein at least one of the 4 amino acids is an aromatic amino acid.

According to further features in preferred embodiments of the inventiondescribed below, the device further comprises a substrate having afluorescent powder coating, the fluorescent powder coating being capableof emitting light upon activation by the electrons.

According to still a further aspect of the present invention there isprovided a device for obtaining information from a nanoscaleenvironment, the device comprising: (a) a nanowire capable of collectingsignals from the nanoscale environment, the nanowire being formed of aconducting material, at least partially enclosed by a nanostructurecomposed of a plurality of peptides each including no more than 4 aminoacids, wherein at least one of the 4 amino acids is an aromatic aminoacid; and (b) a detection system capable of interfacing with thenanowire and receiving the signals thus obtaining information from thenanoscale environment; and

According to further features in preferred embodiments of the inventiondescribed below, the device further comprises a supporting element ontowhich the nanowire being mounted, wherein the supporting element isoperable to physically scan the nanoscale environment.

According to still a further aspect of the present invention there isprovided an apparatus for electron emission lithography, comprising: (a)an electron emission source being at a first electrical potential, theelectron emission source including at least one nanowire, each of the atleast one nanowire being formed of a conducting material, at leastpartially enclosed by a nanostructure composed of a plurality ofpeptides, each including no more than 4 amino acids, wherein at leastone of the 4 amino acids is an aromatic amino acid; (b) an electricallyconducting mounting device being in a second electrical potential, thesecond electrical potential being different from the first electricalpotential; wherein a difference between the second electrical potentialand the first electrical potential is selected such that electrons areemitted from the electron emission source, and impinge on the mountingdevice to thereby perform a lithography process on a sample mounted onthe mounting device.

According to further features in preferred embodiments of the inventiondescribed below, the apparatus further comprises a magnetic fieldgenerator for generating a magnetic field, thereby to direct theelectrons to a predetermined location on the sample.

According to still a further aspect of the present invention there isprovided a nanoscale mechanical device, comprising at least onenanostructure device designed and configured for grabbing and/ormanipulating nanoscale objects, wherein the at least one nanostructuredevice is formed of a conducting material, at least partially enclosedby a nanostructure composed of a plurality of peptides, each includingno more than 4 amino acids, wherein at least one of the 4 amino acids isan aromatic amino acid.

According to further features in preferred embodiments of the inventiondescribed below, the at least one nanostructure device comprise a firsttubular nanostructure device and a second tubular nanostructure device,the first and the second tubular nanostructure devices being capable ofat least a constrained motion.

According to still further features in the described preferredembodiments the device further comprises a voltage source for generatingelectrostatic force between the first and the second tubularnanostructure devices, thereby to close or open the first and the secondtubular nanostructure devices on the nanoscale object.

According to still a further aspect of the present invention there isprovided an electronic switching or amplifying device, comprising asource electrode, a drain electrode, a gate electrode and a channel,wherein at least one of the gate electrode and the channel comprises ananowire being formed of a conducting or semiconducting material, atleast partially enclosed by a nanostructure composed of a plurality ofpeptides, each including no more than 4 amino acids, wherein at leastone of the 4 amino acids is an aromatic amino acid.

According to still a further aspect of the present invention there isprovided an electronic inverter having a first switching device and asecond switching device, each of the first switching device and thefirst switching device comprising a source electrode, a drain electrode,a gate electrode and a channel, such that the drain electrode of thefirst switching device is electrically communicating with the sourceelectrode of the second switching device; wherein at least one of thegate electrode and the channel comprises a nanowire being formed of aconducting or semiconducting material, at least partially enclosed by ananostructure composed of a plurality of peptides, each including nomore than 4 amino acids, wherein at least one of the 4 amino acids is anaromatic amino acid.

According to still a further aspect of the present invention there isprovided a method of emitting electrons, the method comprising formingan electric field near a nanowire, such that electrons are emittedtherefrom, wherein the nanowire is formed of a conducting material, atleast partially enclosed by a nanostructure composed of a plurality ofpeptides, each including no more than 4 amino acids, wherein at leastone of the 4 amino acids is an aromatic amino acid.

According to still a further aspect of the present invention there isprovided a method of obtaining information from a nanoscale environment,the method comprising: (a) collecting signals from the nanoscaleenvironment using a nanowire, the nanowire being formed of a conductingmaterial, at least partially enclosed by a nanostructure composed of aplurality of peptides, each including no more than 4 amino acids,wherein at least one of the 4 amino acids is an aromatic amino acid; and(b) receiving the signals from the nanowire, thus obtaining informationfrom the nanoscale environment.

According to further features in preferred embodiments of the inventiondescribed below, the method further comprises physically scanning thenanoscale environment using the nanowire.

According to still further features in the described preferredembodiments the information signals are selected from the groupconsisting of mechanical signals, optical signals, electrical signals,magnetic signals, and chemical signals.

According to still further features in the described preferredembodiments the information signals comprise near field light from thenanoscale environment.

According to still further features in the described preferredembodiments the method further comprises converting physical motion ofthe nanowire to electric signals.

According to still a further aspect of the present invention there isprovided a method of electron emission lithography, the methodcomprising: (a) using an electron emission source for emittingelectrons, at least one nanowire, each of the at least one nanowirebeing formed of a conducting material, at least partially enclosed by ananostructure composed of a plurality of peptides, each including nomore than 4 amino acids, wherein at least one of the 4 amino acids is anaromatic amino acid; and (b) collecting the electrons on an electricallyconducting mounting device, thereby performing a lithography process ona sample mounted on the mounting device.

According to further features in preferred embodiments of the inventiondescribed below, the method further comprises generating a magneticfield to thereby direct the electrons to a predetermined location on thesample.

According to still a further aspect of the present invention there isprovided a method of recording binary information, the binaryinformation being composed of a first type of datum and a second type ofdatum, the method comprising using a plurality of nanowires, eachcapable of assuming one of two states, wherein a first state of the twostates correspond to the first type of datum and the second state of thetwo states correspond to the second type of datum; each of the pluralityof nanowires is formed of a conducting material, at least partiallyenclosed by a nanostructure composed of a plurality of peptides, eachincluding no more than 4 amino acids, wherein at least one of the 4amino acids is an aromatic amino acid.

According to still a further aspect of the present invention there isprovided a method of grabbing and/or manipulating nanoscale objects, themethod comprising: (a) providing at least one nanowire, formed of aconducting material, at least partially enclosed by a nanostructurecomposed of a plurality of peptides, each including no more than 4 aminoacids, wherein at least one of the 4 amino acids is an aromatic aminoacid; and (b) using the at least one nanowire for grabbing and/ormanipulating the nanoscale objects.

According to further features in preferred embodiments of the inventiondescribed below, the at least one nanowire comprise a first nanowire anda second nanowire, the first and the second nanowires being capable ofat least a constrained motion.

According to still further features in the described preferredembodiments the method further comprises generating electrostatic forcebetween the first and the second tubular nanowires, thereby closing oropening the first and the second nanowires on the nanoscale object.

According to still a further aspect of the present invention there isprovided a method of cooling an object, the method comprising, (a)absorbing heat from the object using a first heat conducting layer; (b)transporting the heat away from the first heat conducting layer througha plurality of nanowires being under a potential difference; and (c)dissipating the heat over a second heat conducting layer; wherein eachof the plurality of nanowires is formed of a thermoelectric material atleast partially enclosed by a nanostructure composed of a plurality ofpeptides, and wherein each of the plurality of peptides includes no morethan 4 amino acids, such that at least one of the 4 amino acids is anaromatic amino acid.

According to still further features in the described preferredembodiments the nanostructure does not exceed 500 nm in diameter.

According to still further features in the described preferredembodiments the tubular nanostructure is at least 1 nm in length.

According to still further features in the described preferredembodiments each of the 4 amino acids is independently selected from thegroup of naturally occurring amino acids, synthetic amino acids, β-aminoacids, Peptide Nucleic Acid (PNA) and combinations thereof.

According to still further features in the described preferredembodiments at least one of the 4 amino acids is a D-amino acid.

According to still further features in the described preferredembodiments at least one of the 4 amino acids is an L-amino acid.

According to still further features in the described preferredembodiments at least one of the peptide nanostructures comprises atleast two aromatic moieties.

According to still further features in the described preferredembodiments at least one of the peptide nanostructures is ahomodipeptide. According to still further features in the describedpreferred embodiments each of the amino acids is the homodipeptidecomprises an aromatic moiety, such as, but not limited to, substitutednaphthalenyl, unsubstituted naphthalenyl, substituted phenyl orunsubstituted phenyl.

According to still further features in the described preferredembodiments the substituted phenyl is selected from the group consistingof pentafluoro phenyl, iodophenyl, biphenyl and nitrophenyl.

Thus, representative examples of the amino acids in the homopeptideinclude, without limitation, naphthylalanine, p-nitro-phenylalanine,iodo-phenylalanine and fluoro-phenylalanine.

according to still further features in the described preferredembodiments the homodipeptide is selected from the group consisting ofnaphthylalanine-naphthylalanine dipeptide,(pentafluoro-phenylalanine)-(pentafluoro-phenylalanine) dipeptide,(iodo-phenylalanine)-(iodo-phenylalanine) dipeptide, (4-phenylphenylalanine)-(4-phenyl phenylalanine) dipeptide and(p-nitro-phenylalanine)-(p-nitro-phenylalanine) dipeptide.

According to still further features in the described preferredembodiments the nanostructure is stable at a temperature range of 4-400°C.

According to still further features in the described preferredembodiments the nanostructure is stable in an acidic environment.

According to still further features in the described preferredembodiments the nanostructure is stable in a basic environment.

According to still further features in the described preferredembodiments the polyaromatic peptides are at least 5 amino acids inlength.

According to still further features in the described preferredembodiments the polyaromatic peptides are selected from the groupconsisting of polyphenylalanine peptides, polytriptophane peptides,polytyrosine peptides, non-natural derivatives thereof and combinationsthereof.

According to still further features in the described preferredembodiments the material is in a gaseous state.

According to still further features in the described preferredembodiments the material is in a condensed state.

According to still further features in the described preferredembodiments the material is selected from the group consisting of aconducting material, a semiconducting material, a thermoelectricmaterial, a magnetic material, a light-emitting material, a biomineral,a polymer and an organic material.

According to still further features in the described preferredembodiments conducting material is selected from the group consisting ofsilver, gold, copper, platinum, nickel and palladium.

According to still further features in the described preferredembodiments the biomineral comprises calcium carbonate.

According to still further features in the described preferredembodiments the polymer is selected from the group consisting ofpolyethylene, polystyrene and polyvinyl chloride.

According to still further features in the described preferredembodiments the biomolecule is selected from the group consisting of apolynucleotide and a polypeptide.

According to still further features in the described preferredembodiments the light-emitting material is selected from the groupconsisting of dysprosium, europium, terbium, ruthenium, thulium,neodymium, erbium, ytterbium and any organic complex thereof.

According to still further features in the described preferredembodiments the thermoelectric material is selected from the groupconsisting of bismuth telluride, bismuth selenide, antimony telluride,bismuth antimony telluride and bismuth selenium telluride.

According to still further features in the described preferredembodiments the magnetic material is a paramagnetic material.

According to still further features in the described preferredembodiments the paramagnetic material is selected from the groupconsisting of cobalt, copper, nickel and platinum.

According to still further features in the described preferredembodiments the magnetic material is a ferromagnetic material.

According to still further features in the described preferredembodiments the ferromagnetic material is selected from the groupconsisting of magnetite and NdFeB.

According to still further features in the described preferredembodiments the semiconducting material is selected from the groupconsisting of CdS, CdSe, ZnS and SiO₂.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing a peptide nanostructureencapsulating foreign materials, which can be used in variousapplications such as, but not limited to, electric, diagnostic,therapeutic, photonic, mechanic, acoustic and biological application.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. In case of conflict, the patentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and not intendedto be limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIG. 1 is a flowchart diagram of a method of positioning a targetmolecule at a predetermined location, according to a preferredembodiment of the present invention;

FIG. 2 is a flowchart diagram of a method of delivering an agent to asubject according to a preferred embodiment of the present invention;

FIG. 3 is a schematic illustration of a device for obtaining informationfrom a nanoscale environment, according to a preferred embodiment of thepresent invention.

FIGS. 4 a-b are schematic illustrations of a top view (FIG. 4 a) and aside view (FIG. 4 b) of an apparatus for characterizing a nucleic acidsequence of a polynucleotide, according to a preferred embodiment of thepresent invention;

FIG. 5 a is a schematic illustration of a field emitter device,according to a preferred embodiment of the present invention.

FIG. 5 b is a schematic illustration of a matrix of row and columnelectrodes, according to a preferred embodiment of the presentinvention.

FIG. 6 is a schematic illustration of an apparatus for electron emissionlithography, according to a preferred embodiment of the presentinvention.

FIGS. 7 a-b are schematic illustrations of a memory cell, according to apreferred embodiment of the present invention.

FIG. 8 is a schematic illustration of a memory cell, based on magneticnanowires, according to a preferred embodiment of the present invention;

FIG. 9 a is a schematic illustration of an electronic device forswitching, inverting or amplifying, according to a preferred embodimentof the present invention.

FIG. 9 b is a schematic illustration of an inverter, which is formedfrom two devices, each similar to the device of FIG. 5 a, according to apreferred embodiment of the present invention.

FIG. 10 a is a schematic illustration of a transistor, formed of twonanowires, according to a preferred embodiment of the present invention;

FIG. 10 b is a schematic illustration of an array of junctions, eachdefined between two nanowires, according to a preferred embodiment ofthe present invention;

FIG. 11 is a schematic illustration of an electronic circuit assembly,according to a preferred embodiment of the present invention;

FIGS. 12 a-b are schematic illustrations of a device for detecting aposition and/or movement of an object, according to a preferredembodiment of the present invention;

FIG. 13 is a schematic illustration of a display system, according to apreferred embodiment of the present invention;

FIG. 14 is a schematic illustration of a thermoelectric device,according to a preferred embodiment of the present invention;

FIG. 15 is a schematic illustration of another thermoelectric device,according to a preferred embodiment of the present invention;

FIG. 16 is a schematic illustration of a nanoscale mechanical device forgriping and/or manipulating objects of nanometric size, according to apreferred embodiment of the present invention.

FIG. 17 is a photomicrograph depicting self-assembly of well-ordered andelongated peptide nanotubes by a molecular recognition motif derivedfrom the β-amyloid polypeptide. The TEM image shows negatively-stainednanotubes formed by the diphenylalanine peptide.

FIGS. 18 a-c are graphs showing the results of Energy-dispersive x-rayanalysis (EDX) on various peptide-material composites. EDX analysis wasperformed using a Philips Tecnai F20 Field Emission Gun-TransmissionElectron Microscope (FEG-TEM) equipped with EDAX detector. FIG. 18a—shows EDX analysis effected on uranyl acetate filled peptidenanotubes. FIG. 18 b—shows EDX analysis effected on silver filledpeptide nanotubes. FIG. 18 c—shows EDX analysis effected on Silvernanowires.

FIGS. 19 a-d are photomicrographs depicting the casting of silvernanowires with the peptide nanotubes. FIG. 19 a is a schematicillustration depicting the formation of a nanowire. FIG. 19 b is a TEMimage (without staining) of peptide tubes filled with silver nanowires.FIGS. 19 c-d are TEM images of silver nanowires obtained following theaddition of the Proteinase K enzyme to the nanotube solution. Size baris indicated at the right of each image.

FIG. 20 is a schematic illustration of a chemical structure of anaphthylalanine-naphthylalanine (Nal-Nal) dipeptide.

FIG. 21 is an electron microscope image of Nal-Nal tubularnanostructures.

FIGS. 22A-D are electron microscope images of tubular and planarnanostructures assembled from the following aromatic-homodipeptides:(Pentafluoro-phenylalanine)-(pentafluoro-phenylalanine) (FIG. 22A),(iodo-phenylalanine)-(iodo-phenylalanine) (FIG. 22B), (4-phenylphenylalanine)-(4-phenyl phenylalanine) (FIG. 22C), and(p-nitro-phenylalanine)-(p-nitro-phenylalanine) (FIG. 22D).

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of a peptide nanostructure encapsulatingforeign materials. Specifically, the present invention can be used innumerous applications, such as, but not limited to, field effecttransistors, bipolar transistors, complementary inverters, tunneldiodes, light emitting diodes, sensors, display systems and devices,memory chips, cooling systems, nano-mechanical devices and the like. Thepeptide nanostructure can also be used in numerous medical andbiological applications, such as, but not limited to, drug delivery,molecule monitoring and locomotion, nucleic acid sequencing and thelike.

The principles and operation of the present invention may be betterunderstood with reference to the drawings and accompanying descriptions.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details set forth in the following description or exemplified bythe Examples. The invention is capable of other embodiments or of beingpracticed or carried out in various ways. Also, it is to be understoodthat the phraseology and terminology employed herein is for the purposeof description and should not be regarded as limiting.

Self-assembled nanostructures allow controlled fabrication of novelnanoscopic materials and devices. Nanotubular structures areparticularly important as they may serve as nanowires and nanoscaffoldsin numerous applications. Most widely used nanotubes are made of carbonor peptide assemblers (i.e., building blocks). While carbon nanotubes,suffer from major structural defects including branching and bendingresulting in spatial structures with unpredictable electronic, molecularand structural properties, peptide nanotubes such as those composed ofsurfactant like peptides and cyclic D-, L-peptide subunits formcrystals, networks, or bundles of nanostructures and thus can not beused in the above-described applications.

While reducing the present invention to practice, the present inventorsuncovered that aromatic peptides (e.g., diphenylalanine) are capable offorming tubular and spherical nanostructures, which can be used innumerous mechanical, electrical, chemical, optical and biotechnologicalsystems.

Although the term nanotubes was previously attributed to hollownanometric channels, which are formed within the macroscopic crystalstructure of diphenylalanine peptides [Gorbitz (2001) Chemistry 38:6791]these so called ‘nanotubes’ are structurally different from theindividual nanostructures formed by the present invention.

The difference in structure can be explained by the different conditionswhich were used to assemble the structures. While Gorbitz allowedcrystallization by evaporation of an aqueous peptide solution in hightemperature (i.e., 80° C.), the present inventors allowed self-assemblyin an aqueous solution under mild-conditions (see Example 1 of theExamples section which follows).

Thus, according to one aspect of the present invention, there isprovided a tubular, spherical or planar nanostructure. The nanostructureof this aspect of the present invention is composed of a plurality ofpeptides, each peptide including no more than 4 amino acids of which atleast one is an aromatic amino acid.

As used herein the phrase “tubular, spherical or planar nanostructure”refers to a planar (e.g., disk-shape), spherical or elongated tubular orconical structure having a diameter or a cross-section of less than 1 μm(preferably less than 500 nm, more preferably less than about 50 nm,even more preferably less than about 5 nm). The length of the tubularnanostructure of the present invention is preferably at least 1 μm, morepreferably at least 10 nm, even more preferably at least 100 nm and evenmore preferably at least 500 nm. It will be appreciated, though, thatthe tubular structure of the present invention can be of infinite length(i.e., macroscopic fibrous structures) and as such can be used in thefabrication of hyper-strong materials.

The nanostructure of the present invention is preferably hollow and canbe either conductive, semi-conductive or non-conductive.

According to a preferred embodiment of this aspect of the presentinvention the peptide is a dipeptide or a tripeptide such as set forthin SEQ ID NO: 1, 5, 6, 7 or 8 (see the Examples section which follows).Depending on the rigidity of the molecular structure of the peptideused, tubular or spherical nanostructures are formed. Thus, for examplea plurality of diphenylglycine peptides, which offer similar molecularproperties as diphenylalenine peptides albeit with a lower degree ofrotational freedom around the additional C—C bond and a higher sterichindrance will self-assemble into nano spheres, while a plurality ofdiphenylalenine peptides will self-assemble into nanotubes.

The present invention also envisages nanostructures which are composedof a plurality of polyaromatic peptides being longer than the abovedescribed (e.g., 50-136 amino acids).

As used herein the phrase “polyaromatic peptides” refers to peptideswhich include at least 80%, at least 85% at least 90%, at least 95% ormore, say 100% aromatic amino acid residues. These peptides can behomogenic (e.g., polyphenylalanine, see Example 3 of the Examplessection which follows) or heterogenic of at least 5, at least 10, atleast 15, at least 20, at least 25, at least 30, at least 35, at least40, at least 45, at least 50, at least 55, at least 60, at least 65, atleast 70, at least 75, at least 80, at least 85, at least 90, at least95, at least 100, at least 105, at least 110, at least 120, at least125, at least 130, at least 135, at least 140, at least 145, at least150, at least 155, at least 160, at least 170, at least 190, at least200, at least 300, at least 500 amino acids.

The term “peptide” as used herein encompasses native peptides (eitherdegradation products, synthetically synthesized peptides or recombinantpeptides) and peptidomimetics (typically, synthetically synthesizedpeptides), as well as peptoids and semipeptoids which are peptideanalogs, which may have, for example, modifications rendering thepeptides more stable while in a body or more capable of penetrating intocells. Such modifications include, but are not limited to N terminusmodification, C terminus modification, peptide bond modification,including, but not limited to, CH2-NH, CH2-S, CH2-S═O, O═C—NH, CH2-O,CH2-CH2, S═C—NH, CH═CH or CF═CH, backbone modifications, and residuemodification. Methods for preparing peptidomimetic compounds are wellknown in the art and are specified, for example, in Quantitative DrugDesign, C. A. Ramsden Gd., Chapter 17.2, F. Choplin Pergamon Press(1992), which is incorporated by reference as if fully set forth herein.Further details in this respect are provided hereinunder.

Peptide bonds (—CO—NH—) within the peptide may be substituted, forexample, by N-methylated bonds (—N(CH3)-CO—), ester bonds(—C(R)H—C—O—O—C(R)—N—), ketomethylene bonds (—CO—CH2-), α-aza bonds(—NH—N(R)—CO—), wherein R is any alkyl, e.g., methyl, carba bonds(—CH2-NH—), hydroxyethylene bonds (—CH(OH)—CH2-), thioamide bonds(—CS—NH—), olefinic double bonds (—CH═CH—), retro amide bonds (—NH—CO—),peptide derivatives (—N(R)—CH2-CO—), wherein R is the “normal” sidechain, naturally presented on the carbon atom.

These modifications can occur at any of the bonds along the peptidechain and even at several (2-3) at the same time.

Natural aromatic amino acids, Trp, Tyr and Phe, may be substituted forsynthetic non-natural acid such as Phenylglycine, TIC, naphthylalanine(Nal), ring-methylated derivatives of Phe, halogenated derivatives ofPhe or o-methyl-Tyr, and β amino-acids.

In addition to the above, the peptides of the present invention may alsoinclude one or more modified amino acids (e.g., thiolated amino acids,see Example 2 of the Examples section, or biotinylated amino acids) orone or more non-amino acid monomers (e.g. fatty acids, complexcarbohydrates etc). Also contemplated are homodipeptides, and morepreferably aromatic homodipeptides in which each of the amino acidscomprises an aromatic moiety, such as, but not limited to, substitutedor unsubstituted naphthalenyl and substituted or unsubstituted phenyl.The aromatic moiety can alternatively be substituted or unsubstitutedheteroaryl such as, for example, indole, thiophene, imidazole, oxazole,thiazole, pyrazole, pyridine, pyrimidine, quinoline, isoquinoline,quinazoline, quinoxaline, and purine

When substituted, the phenyl, naphthalenyl or any other aromatic moietyincludes one or more substituents such as, but not limited to, alkyl,trihaloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl,heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy, thiohydroxy,thioalkoxy, cyano, and amine.

As used herein, the term “alkyl” refers to a saturated aliphatichydrocarbon including straight chain and branched chain groups.Preferably, the alkyl group has 1 to 20 carbon atoms. The alkyl groupmay be substituted or unsubstituted. When substituted, the substituentgroup can be, for example, trihaloalkyl, alkenyl, alkynyl, cycloalkyl,aryl, heteroaryl, heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy,thiohydroxy, thioalkoxy, cyano, and amine.

A “cycloalkyl” group refers to an all-carbon monocyclic or fused ring(i.e., rings which share an adjacent pair of carbon atoms) group whereinone of more of the rings does not have a completely conjugatedpi-electron system. Examples, without limitation, of cycloalkyl groupsare cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane,cyclohexadiene, cycloheptane, cycloheptatriene, and adamantane. Acycloalkyl group may be substituted or unsubstituted. When substituted,the substituent group can be, for example, alkyl, trihaloalkyl, alkenyl,alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, nitro,azo, hydroxy, alkoxy, thiohydroxy, thioalkoxy, cyano, and amine.

An “alkenyl” group refers to an alkyl group which consists of at leasttwo carbon atoms and at least one carbon-carbon double bond.

An “alkynyl” group refers to an alkyl group which consists of at leasttwo carbon atoms and at least one carbon-carbon triple bond.

An “aryl” group refers to an all-carbon monocyclic or fused-ringpolycyclic (i.e., rings which share adjacent pairs of carbon atoms)groups having a completely conjugated pi-electron system. Examples,without limitation, of aryl groups are phenyl, naphthalenyl andanthracenyl. The aryl group may be substituted or unsubstituted. Whensubstituted, the substituent group can be, for example, alkyl,trihaloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl,heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy, thiohydroxy,thioalkoxy, cyano, and amine.

A “heteroaryl” group refers to a monocyclic or fused ring (i.e., ringswhich share an adjacent pair of atoms) group having in the ring(s) oneor more atoms, such as, for example, nitrogen, oxygen and sulfur and, inaddition, having a completely conjugated pi-electron system. Examples,without limitation, of heteroaryl groups include pyrrole, furane,thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrimidine,quinoline, isoquinoline and purine. The heteroaryl group may besubstituted or unsubstituted. When substituted, the substituent groupcan be, for example, alkyl, trihaloalkyl, alkenyl, alkynyl, cycloalkyl,aryl, heteroaryl, heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy,thiohydroxy, thioalkoxy, cyano, and amine.

A “heteroalicyclic” group refers to a monocyclic or fused ring grouphaving in the ring(s) one or more atoms such as nitrogen, oxygen andsulfur. The rings may also have one or more double bonds. However, therings do not have a completely conjugated pi-electron system. Theheteroalicyclic may be substituted or unsubstituted. When substituted,the substituted group can be, for example, lone pair electrons, alkyl,trihaloalkyl, alkenyl, alkynyl, cycloalkyl, Aryl, heteroaryl,heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy, thiohydroxy,thioalkoxy, cyano, and amine. Representative examples are piperidine,piperazine, tetrahydro furane, tetrahydropyrane, morpholino and thelike.

A “hydroxy” group refers to an —OH group.

An “azide” group refers to a —N═N≡N group.

An “alkoxy” group refers to both an —O-alkyl and an —O-cycloalkyl group,as defined herein.

An “aryloxy” group refers to both an —O-aryl and an —O-heteroaryl group,as defined herein.

A “thiohydroxy” group refers to an —SH group.

A “thioalkoxy” group refers to both an —S-alkyl group, and an—S-cycloalkyl group, as defined herein.

A “thioaryloxy” group refers to both an —S-aryl and an —S-heteroarylgroup, as defined herein.

A “halo” group refers to fluorine, chlorine, bromine or iodine.

A “trihaloalkyl” group refers to an alkyl substituted by three halogroups, as defined herein. A representative example is trihalomethyl.

An “amino” group refers to an —NR′R″ group where R′ and R″ are hydrogen,alkyl, cycloalkyl or aryl.

A “nitro” group refers to an —NO₂ group.

A “cyano” group refers to a —C≡N group.

Representative examples of such homodipeptides include, withoutlimitation, a naphthylalanine-naphthylalanine (Nal-Nal) dipeptides (SEQID NO: 9), (pentafluoro-phenylalanine)-(pentafluoro-phenylalanine) (SEQID NO: 10), (iodo-phenylalanine)-(iodo-phenylalanine) (SEQ ID NO: 11),(4-phenyl phenylalanine)-(4-phenyl phenylalanine) (SEQ ID NO: 12) and(p-nitro-phenylalanine)-(p-nitro-phenylalanine) (SEQ ID NO: 13) (seeExample 4-5 and FIGS. 20-22).

As used herein in the specification and in the claims section below theterm “amino acid” or “amino acids” is understood to include the 20naturally occurring amino acids; those amino acids often modifiedpost-translationally in vivo, including, for example, hydroxyproline,phosphoserine and phosphothreonine; and other unusual amino acidsincluding, but not limited to, 2-aminoadipic acid, hydroxylysine,isodesmosine, nor-valine, nor-leucine and ornithine. Furthermore, theterm “amino acid” includes both D- and L-amino acids.

Tables 1 and 2 below list naturally occurring amino acids (Table 1) andnon-conventional or modified amino acids (Table 2) which can be usedwith the present invention.

TABLE 1 Amino Acid Three-Letter Abbreviation One-letter Symbol alanineAla A Arginine Arg R Asparagine Asn N Aspartic acid Asp D Cysteine Cys CGlutamine Gln Q Glutamic Acid Glu E glycine Gly G Histidine His Hisoleucine Iie I leucine Leu L Lysine Lys K Methionine Met Mphenylalanine Phe F Proline Pro P Serine Ser S Threonine Thr Ttryptophan Trp W tyrosine Tyr Y Valine Val V Any amino acid as Xaa Xabove

TABLE 2 Non-conventional amino acid Code α-aminobutyric acid Abuα-amino-α-methylbutyrate Mgabu aminocyclopropane- Cpro carboxylateaminoisobutyric acid Aib aminonorbornyl- Norb carboxylatecyclohexylalanine Chexa cyclopentylalanine Cpen D-alanine Dal D-arginineDarg D-aspartic acid Dasp D-cysteine Dcys D-glutamine Dgln D-glutamicacid Dglu D-histidine Dhis D-isoleucine Dile D-leucine Dleu D-lysineDlys D-methionine Dmet D-ornithine Dorn D-phenylalanine Dphe D-prolineDpro D-serine Dser D-threonine Dthr D-tryptophan Dtrp D-tyrosine DtyrD-valine Dval D-α-methylalanine Dmala D-α-methylarginine DmargD-α-methylasparagine Dmasn D-α-methylaspartate Dmasp D-α-methylcysteineDmcys D-α-methylglutamine Dmgln D-α-methylhistidine DmhisD-α-methylisoleucine Dmile D-α-methylleucine Dmleu D-α-methyllysineDmlys D-α-methylmethionine Dmmet D-α-methylornithine DmornD-α-methylphenylalanine Dmphe D-α-methylproline Dmpro D-α-methylserineDmser D-α-methylthreonine Dmthr D-α-methyltryptophan DmtrpD-α-methyltyrosine Dmty D-α-methylvaline Dmval D-α-methylalnine DnmalaD-α-methylarginine Dnmarg D-α-methylasparagine DnmasnD-α-methylasparatate Dnmasp D-α-methylcysteine Dnmcys D-N-methylleucineDnmleu D-N-methyllysine Dnmlys N-methylcyclohexylalanine NmchexaD-N-methylornithine Dnmorn N-methylglycine Nala N-methylaminoisobutyrateNmaib N-(1-methylpropyl)glycine Nile N-(2-methylpropyl)glycine NileN-(2-methylpropyl)glycine Nleu D-N-methyltryptophan DnmtrpD-N-methyltyrosine Dnmtyr D-N-methylvaline Dnmval γ-aminobutyric acidGabu L-t-butylglycine Tbug L-ethylglycine Etg L-homophenylalanine HpheL-α-methylarginine Marg L-α-methylaspartate Masp L-α-methylcysteine McysL-α-methylglutamine Mgln L-α-methylhistidine Mhis L-α-methylisoleucineMile D-N-methylglutamine Dnmgln D-N-methylglutamate DnmgluD-N-methylhistidine Dnmhis D-N-methylisoleucine Dnmile D-N-methylleucineDnmleu D-N-methyllysine Dnmlys N-methylcyclohexylalanine NmchexaD-N-methylornithine Dnmorn N-methylglycine Nala N-methylaminoisobutyrateNmaib N-(1-methylpropyl)glycine Nile N-(2-methylpropyl)glycine NleuD-N-methyltryptophan Dnmtrp D-N-methyltyrosine Dnmtyr D-N-methylvalineDnmval γ-aminobutyric acid Gabu L-t-butylglycine Tbug L-ethylglycine EtgL-homophenylalanine Hphe L-α-methylarginine Marg L-α-methylaspartateMasp L-α-methylcysteine Mcys L-α-methylglutamine MglnL-α-methylhistidine Mhis L-α-methylisoleucine Mile L-α-methylleucineMleu L-α-methylmethionine Mmet L-α-methylnorvaline MnvaL-α-methylphenylalanine Mphe L-α-methylserine mser L-α-methylvaline MtrpL-α-methylleucine Mval Nnbhm N-(N-(2,2-diphenylethyl)carbamylmethyl-glycine Nnbhm 1-carboxy-1-(2,2-diphenyl Nmbcethylamino)cyclopropane L-N-methylalanine Nmala L-N-methylarginine NmargL-N-methylasparagine Nmasn L-N-methylaspartic acid NmaspL-N-methylcysteine Nmcys L-N-methylglutamine Nmgin L-N-methylglutamicacid Nmglu L-N-methylhistidine Nmhis L-N-methylisolleucine NmileL-N-methylleucine Nmleu L-N-methyllysine Nmlys L-N-methylmethionineNmmet L-N-methylnorleucine Nmnle L-N-methylnorvaline NmnvaL-N-methylornithine Nmorn L-N-methylphenylalanine NmpheL-N-methylproline Nmpro L-N-methylserine Nmser L-N-methylthreonine NmthrL-N-methyltryptophan Nmtrp L-N-methyltyrosine Nmtyr L-N-methylvalineNmval L-N-methylethylglycine Nmetg L-N-methyl-t-butylglycine NmtbugL-norleucine Nle L-norvaline Nva α-methyl-aminoisobutyrate Maibα-methyl-γ-aminobutyrate Mgabu α-methylcyclohexylalanine Mchexaα-methylcyclopentylalanine Mcpen α-methyl-α-napthylalanine Manapα-methylpenicillamine Mpen N-(4-aminobutyl)glycine NgluN-(2-aminoethyl)glycine Naeg N-(3-aminopropyl)glycine NornN-amino-α-methylbutyrate Nmaabu α-napthylalanine Anap N-benzylglycineNphe N-(2-carbamylethyl)glycine Ngln N-(carbamylmethyl)glycine NasnN-(2-carboxyethyl)glycine Nglu N-(carboxymethyl)glycine NaspN-cyclobutylglycine Ncbut N-cycloheptylglycine Nchep N-cyclohexylglycineNchex N-cyclodecylglycine Ncdec N-cyclododeclglycine NcdodN-cyclooctylglycine Ncoct N-cyclopropylglycine NcproN-cycloundecylglycine Ncund N-(2,2-diphenylethyl)glycine NbhmN-(3,3-diphenylpropyl)glycine Nbhe N-(3-indolylyethyl) glycine NhtrpN-methyl-γ-aminobutyrate Nmgabu D-N-methylmethionine DnmmetN-methylcyclopentylalanine Nmcpen D-N-methylphenylalanine DnmpheD-N-methylproline Dnmpro D-N-methylserine Dnmser D-N-methylserine DnmserD-N-methylthreonine Dnmthr N-(1-methylethyl)glycine NvaN-methyla-napthylalanine Nmanap N-methylpenicillamine NmpenN-(p-hydroxyphenyl)glycine Nhtyr N-(thiomethyl)glycine Ncyspenicillamine Pen L-α-methylalanine Mala L-α-methylasparagine MasnL-α-methyl-t-butylglycine Mtbug L-methylethylglycine MetgL-α-methylglutamate Mglu L-α-methylhomo phenylalanine MhpheN-(2-methylthioethyl)glycine Nmet N-(3-guanidinopropyl)glycine NargN-(1-hydroxyethyl)glycine Nthr N-(hydroxyethyl)glycine NserN-(imidazolylethyl)glycine Nhis N-(3-indolylyethyl)glycine NhtrpN-methyl-γ-aminobutyrate Nmgabu D-N-methylmethionine DnmmetN-methylcyclopentylalanine Nmcpen D-N-methylphenylalanine DnmpheD-N-methylproline Dnmpro D-N-methylserine Dnmser D-N-methylthreonineDnmthr N-(1-methylethyl)glycine Nval N-methyla-napthylalanine NmanapN-methylpenicillamine Nmpen N-(p-hydroxyphenyl)glycine NhtyrN-(thiomethyl)glycine Ncys penicillamine Pen L-α-methylalanine MalaL-α-methylasparagine Masn L-α-methyl-t-butylglycine MtbugL-methylethylglycine Metg L-α-methylglutamate MgluL-α-methylhomophenylalanine Mhphe N-(2-methylthioethyl)glycine NmetL-α-methyllysine Mlys L-α-methylnorleucine Mnle L-α-methylornithine MornL-α-methylproline Mpro L-α-methylthreonine Mthr L-α-methyltyrosine MtyrL-N-methylhomophenylalanine Nmhphe N-(N-(3,3-diphenylpropyl)carbamylmethyl(1)glycine Nnbhe

The nanostructures of the present invention are preferably generated byallowing a highly concentrated aqueous solution of the peptides of thepresent invention to self-assemble under mild conditions as detailed inthe Examples section which follows.

The resulting nanostructures are preferably stable under acidic and/orbasic pH conditions, a wide range of temperatures (e.g., 4-400° C., morepreferably, 4-200° C.) and/or proteolytic conditions (i.e., proteinaseK).

According to preferred embodiments of the present invention, thenanostructures are filled or partially filled with at least one material(i.e., the nanostructure enclose or partially enclose the material).

The material can be composed of a conducting material, a semiconductingmaterial, a thermoelectric material, a magnetic material (paramagnetic,ferromagnetic or diamagnetic), a light-emitting material, a gaseousmaterial, a biomineral, a polymer and/or an organic material.

For example, the nanostructures may enclose conducting or semiconductingmaterials, including, without limitation, inorganic structures such asGroup IV, Group III/Group V, Group II/Group VI elements, transitiongroup elements, or the like.

As used herein, the term “Group” is given its usual definition asunderstood by one of ordinary skill in the art. For instance, Group IIelements include Zn, Cd and Hg; Group III elements include B, Al, Ga, Inand Tl; Group IV elements include C, Si, Ge, Sn and Pb; Group V elementsinclude N, P, As, Sb and Bi; and Group VI elements include O, S, Se, Teand Po.

Thus, for conducting materials, the nanostructures may enclose, forexample, silver, gold, copper, platinum, nickel, or palladium. Forsemiconducting materials the nanostructures may enclose, for example,silicon, indium phosphide, gallium nitride and others.

The nanostructures may also encapsulate, for example, any organic orinorganic molecules that are polarizable or have multiple charge states.For example, the nanostructures may include main group and metalatom-based wire-like silicon, transition metal-containing wires, galliumarsenide, gallium nitride, indium phosphide, germanium, or cadmiumselenide structures.

Additionally, the nanostructure of the present invention may enclosevarious combinations of materials, including semiconductors and dopants.Representative examples include, without limitations, silicon,germanium, tin, selenium, tellurium, boron, diamond, or phosphorous. Thedopant may also be a solid solution of various elemental semiconductors,for example, a mixture of boron and carbon, a mixture of boron and P, amixture of boron and silicon, a mixture of silicon and carbon, a mixtureof silicon and germanium, a mixture of silicon and tin, or a mixture ofgermanium and tin. In some embodiments, the dopant or the semiconductormay include mixtures of different groups, such as, but not limited to, amixture of a Group III and a Group V element, a mixture of Group III andGroup V elements, a mixture of Group II and Group VI semiconductors.Additionally, alloys of different groups of semiconductors may also bepossible, for example, a combination of a Group II-Group VI and a GroupIII-Group V semiconductor and a Group I and a Group VII semiconductor.

Specific and representative examples of semiconducting materials whichcan be encapsulated by the nanostructure of the present inventioninclude, without limitation, CdS, CdSe, ZnS and SiO₂.

The nanostructure of the present invention may also enclose athermoelectric material that exhibits a predetermined thermoelectricpower. Preferably, such a material is selected so that the resultingnanostructure composition is characterized by a sufficient figure ofmerit. Such composition, as further detailed hereinunder, may be used inthermoelectric systems and devices as heat transfer media orthermoelectric power sources. According to a preferred embodiment of thepresent invention the thermoelectric material which can be encapsulatedin the nanostructure of the present invention may be a bismuth-basedmaterial, such as, but not limited to, elemental bismuth, a bismuthalloy or a bismuth intermetallic compound. The thermoelectric materialmay also be a mixture of any of the above materials or other materialsknown to have thermoelectric properties. In addition the thermoelectricmaterial may also include a dopant. Representative examples include,without limitation, bismuth telluride, bismuth selenide, bismuthantimony telluride, bismuth selenium telluride and the like. Othermaterials are disclosed, for example, in U.S. Patent Application No.20020170590.

As stated, the nanostructure of the present invention may also enclosemagnetic materials. Generally, all materials in nature posses some kindof magnetic properties which are manifested by a force acting on aspecific material when present in a magnetic field. These magneticproperties, which originate from the sub-atomic structure of thematerial, are different from one substrate to another. The direction aswell as the magnitude of the magnetic force is different for differentmaterials.

Whereas the direction of the force depends only on the internalstructure of the material, the magnitude depends both on the internalstructure as well as on the size (mass) of the material. The internalstructure of the materials in nature, to which the magneticcharacteristics of matter are related, is classified according to one ofthree major groups: diamagnetic, paramagnetic and ferromagneticmaterials, where the strongest magnetic force acts on ferromagneticmaterials.

In terms of direction, the magnetic force acting on a diamagneticmaterial is in opposite direction than that of the magnetic force actingon a paramagnetic or a ferromagnetic material. When placed in externalmagnetic field, a specific material acquires a non-zero magnetic momentper unit volume, also known as a magnetization, which is proportional tothe magnetic field vector. For a sufficiently strong external magneticfield, a ferromagnetic material, due to intrinsic non-local ordering ofthe spins in the material, may retain its magnetization, hence to becomea permanent magnet. As opposed to ferromagnetic materials, bothdiamagnetic and paramagnetic materials loose the magnetization once theexternal magnetic field is switched off.

Representative examples of paramagnetic materials which can be enclosedby the nanostructure of the present invention include, withoutlimitation, cobalt, copper, nickel, and platinum. Representativeexamples of ferromagnetic materials include, without limitation,magnetite and NdFeB.

Other materials which may be encapsulated by the nanostructure of thepresent invention include, without limitation, light-emitting materials(e.g., dysprosium, europium, terbium, ruthenium, thulium, neodymium,erbium, ytterbium or any organic complex thereof), biominerals (e.g.,calcium carbonate) and polymers (e.g., polyethylene, polystyrene,polyvinyl chloride, polynucleotides and polypeptides).

In order to generate the filled nanostructure of the present invention,the foreign material is introduced into the internal cavity of thetubular or spherical nanostructure, to encapsulate the material innanostructure.

A method of filling is described in the Example section which follows,exhibiting casting of nanowires, using as a mold, the nanotubes of thepresent invention.

Other methods of filling nanotubes are described in “Capillarity-inducedfilling of carbon nanotubes”, P M Ajayan et al., Nature, vol. 361, 1993,pp. 333-334; “A simple chemical method of opening and filling carbonnanotubes”, S C Tsang et al., Nature, vol. 372, 1994, pp. 159-162; U.S.Pat. Nos. 5,916,642 and 6,361,861.

Filled nanostructures can be used as such (as further describedhereinbelow), Alternatively, the peptide mold (i.e., nanotube ornanosphere of the present invention), can be removed such as by using aprotease (as further described in the Examples section), to increaseproperties of the casted material, such as conductivity.

Hence, depending on the foreign material present in (encapsulated in)and/or around (coated on, as further described hereinbelow) thenanostructure of the present invention, the peptide nanostructure can bean insulator, a conductor, a semiconductor, thermoelectric, magnetic andthe like. The nanostructure of the present invention can also beutilized as vehicles in which atoms of different materials (e.g.,conducting, semiconducting, magnetic, thermoelectric, chemical orbiological agents) may be enclosed, either in a condensed or in agaseous state.

A detailed description of the nanostructure generated according to theteachings of the present invention follows below, starting first with adescription of the applications of such nanostructures and theadvantages offered thereby.

Generally, the nanostructures of the present invention can be used invarious applications which involve the use of nanoscopic elements. Suchapplications are known in the art and disclosed in U.S. Pat. Nos.5,581,091, 6,383,923, 6,426,134, 6,428,811, 6,428,811, 6,504,292,6,530,944, 6,559,468, 6,579,742, 6,586,095, 6,628,053 and in U.S. PatentApplication Nos. 20020053257, 20020054461, 20020175618, 20020180077,20020187504, 20030089899, 20030096113, 20030121764, 20030141189,20030165074, 20030180491 and 20030197120, which are incorporated hereinby reference.

The nanostructure of the present invention has numerous potentialapplications. Having a substantially high aspect ratio, thenanostructure of the present invention is an ideal candidate for use inprobing application. For example, a nanostructure having a tip diameterof about 10 nm and a length of several micrometers can be used as thetip of an atomic force microscope to probe deep crevices found onintegrated circuits, biological molecules or any other nanoscaleenvironment.

Additionally, the nanostructure of the present invention can be used inthe field of micro- and sub-microelectronic circuitry and devices. Moreparticularly, nanostructure of the present invention can be featurenanoscale wires, referred to herein as nanowires, which can beselectively doped at various locations. The nanowires can be doped, forexample, differentially along their length, or radially, and either interms of identity of dopant, concentration of dopant, or both. This maybe used to provide both n-type and p-type conductivity in a single item,or in different items in close proximity to each other, such as in acrossbar array.

The nanostructure of the present invention can be combined with siliconchips so as to restrict motion of electrons or holes within a nanoscaleregion thereby to provide the system with special electric, opticaland/or chemical characteristics. For example, the use of nanostructureas gates in an electronic device allows operation at low gate voltageand enables the switching of several individual devices on the samesubstrate.

Devices and systems incorporating the nanostructures of the presentinvention may be controlled, for example, using any input signal, suchas an electrical, optical or a magnetic signal. The control may involveswitching between two or more discrete states or may involve continuouscontrol of a nanowire current, i.e., analog control. In addition toelectrical signals, optical signals and magnetic signals, the devicesmay also be controlled in certain embodiments in response to biologicaland chemical species, for example, DNA, protein, metal ions. In a moregeneral sense, the nanostructures of the present invention may becharged or have a dipole moment. In other embodiments, the device may beswitchable in response to mechanical stimuli, for example, mechanicalstretching, vibration and bending. In yet other embodiments, the devicemay be switchable in response to temperature, pressure or fluidmovement, for example, the movement of an environmental gas or liquid.

Following are representative examples of applications in which thenanostructure of the present invention is preferably incorporated.

Referring now to the drawings, FIG. 1 is a flowchart diagram of a methodof positioning a target molecule at a predetermined location. The methodcomprises the following method steps in which in a first step, amagnetic nanowire is provided. The magnetic nanowire is preferablyformed of a magnetic material at least partially enclosed by the peptidenanostructure of the present invention. According to a preferredembodiment of the present invention, the nanostructure has at least onesegment associated with a functional group or ligand, which are capableof binding to the target molecule.

Representative examples of functional groups which are contemplatedinclude, without limitation, thiols, disulfides, cyanides, amines,carboxylic acids, phosphonates, siloxanes or hydroxamic acids.Representative examples of ligands which are contemplated include,without limitation, proteins, fibronectin, DNA, RNA, enzymes, ribozymes,hydrophobic materials, hydrophillic materials, cells, tissue,microorganisms, bacteria, viruses and chemoattractant.

In a second step of the method, the magnetic nanowire is bound to thetarget molecule, and in the third step, the magnetic nanowire (and thetarget molecule to which it bounds) is exposed to a magnetic field. Asstated, when a magnetic material is placed in a magnetic field, itsmagnetic properties are manifested by forces acting thereon. Thus, by ajudicious selection of the magnetic field (magnitude and direction) thenanowire, under the influence of the magnetic force, may be moved,together with the target molecule, to the desired location.

According to another aspect of the present invention, there is provideda method of delivering an agent to a subject. The method comprises thefollowing method steps which are illustrated in the flowchart diagram ofFIG. 2.

Referring to FIG. 2, in a first step of the method, a composition havingthe agent enclosed by the peptide nanostructure of the present inventionis provided, and in a second step, the nanostructure is administrated tothe subject. The present aspect of the invention has numerous ofpotential application in the field of drug delivery, DNA transfection,and other medical and biological applications. The nanostructure of thepresent invention has a particular advantage for these applicationsbecause of its low toxicity, biodegradability.

In this respect, according to a preferred embodiment of the presentinvention the composition may further comprise one or more functionalgroups. In one embodiment, the functional group is an antigen-bindingmoiety, by which is meant a moiety comprising the antigen-recognitionsite of an antibody. Examples of a moiety comprising theantigen-recognition site of an antibody include, but are not limited to,monoclonal antibodies, polyclonal antibodies, Fab fragments ofmonoclonal antibodies, Fab fragments of polyclonal antibodies, Fab₂fragments of monoclonal antibodies, and Fab₂ fragments of polyclonalantibodies. Single chain or multiple chain antigen-recognition sites canbe used. Multiple chain antigen-recognition sites can be fused orunfused.

The antigen-binding moiety can be selected from any known class ofantibodies. Known classes of antibodies include, but are not necessarilylimited to, IgG, IgM, IgA, IgD, and IgE. The various classes also canhave subclasses. For example, known subclasses of the IgG class include,but are not necessarily limited to, IgG1, IgG2, IgG3, and IgG4. Otherclasses have subclasses that are routinely known by one of ordinaryskill in the art.

The antigen-binding moiety can be selected from an antibody derived fromany species. “Derived from,” in this context, can mean either preparedand extracted in vivo from an individual member of a species, orprepared by known biotechnological techniques from a nucleic acidmolecule encoding, in whole or part, an antibody peptide comprisinginvariant regions which are substantially identical to antibodiesprepared in vivo from an individual member of the species or an antibodypeptide recognized by antisera specifically raised against antibodiesfrom the species. Exemplary species include, but are not limited to,human, chimpanzee, baboon, other primate, mouse, rat, goat, sheep, andrabbit, among others known in the art. In one embodiment, the antibodyis chimeric, i.e., comprises a plurality of portions, wherein eachportion is derived from a different species. A chimeric antibody,wherein one of the portions is derived from human, can be considered ahumanized antibody.

Antigen-recognition moieties are available that recognize antigensassociated with a wide variety of cell types, tissues, and organs, and awide variety of medical conditions, in a wide variety of mammalianspecies. Exemplary medical conditions include, but are not limited to,cancers, such as lung cancer, oral cancer, skin cancer, stomach cancer,colon cancer, nervous system cancer, leukemia, breast cancer, cervicalcancer, prostate cancer, and testicular cancer; arthritis; infections,such as bacterial, viral, fungal, or other microbial infections; anddisorders of the skin, the eye, the vascular system, or other celltypes, tissues, or organs.

When the nanostructure of the present invention encapsulates aconducting material, a nanowire is formed. Such a nanowire can be usedas an interface between macroscopic systems and individual objectshaving nanometer dimensions.

Hence, further in accordance with the present invention there isprovided a device for obtaining information from a nanoscaleenvironment. The device according to this aspect of the presentinvention may comprise one or more nanostructures encapsulating aconducting material, which facilitate information exchange between themacroscopic system and the nanoscale environment. Individualnanostructures, nanowires or bundles thereof can be recovered frompeptides, as further detailed hereinabove, in accordance with thepresent invention. Assemblies of nanostructures can be fabricated, forexample, by self-assembly of groups of nanostructures, as furtherdetailed and exemplified in the Examples section that follows.

Referring now to the drawings, FIG. 3 is a schematic illustration of thedevice described above, which is referred to herein as device 10. In itsmost basic form, device 10 comprises a nanowire 12 encapsulating aconducting material (e.g., a nanowire) and a detection system 16.

Nanowire 12 serves for collecting signals from a nanoscale environment14. Any type of signals can be collected by nanowire 12 including,without limitation, mechanical, optical, electrical, magnetic andchemical signals. Detection system 16 serves for interfacing withnanowire 12 and receiving the signals collected thereby. Hence, bycollecting signals using nanowire 12 and detecting the signals usingsystem 16, device 10 is capable of sensing, measuring and analyzingnanoscale environment 14.

According to a preferred embodiment of the present invention device 10may further comprise a supporting element 18 onto which nanowire 12 ismounted. Nanowire 12 is connected to supporting element 18 at one end,with the other end being free and, due to its nanometric dimension,capable of coming into direct contact or near proximity to nanoscaleenvironment 14. Preferably, supporting element 18 can physically scannanoscale environment 14 to thereby allow nanowire 12 to collect signalsfrom, or deliver signals to a plurality of locations of nanoscaleenvironment 14. The “sensing end” of nanowire 12 interacts with objectsbeing sensed, measured or analyzed by means which are (eitherindividually or in combination) physical, electrical, chemical,electromagnetic or biological. This interaction produces forces,electrical currents or chemical compounds which reveal information aboutthe object.

Nanowire 12 and supporting element 18 in combination can essentially beconsidered as a transducer for interacting with nanoscale environment14. Conventional probe microscopy techniques are enabled and improved bythe use of device 10, according to a preferred embodiment of the presentinvention.

Examples of conventional systems of this type include scanning tunnelingmicroscopes, atomic force microscopes, scanning force microscopes,magnetic force microscopes and magnetic resonance force microscopes.

Device 10 is fundamentally different from conventional probe microscopytips in its shape and its mechanical, electronic, chemical and/orelectromagnetic properties. This difference permits new modes ofoperation of many probe microscopes, and new forms of probe microscopy.Device 10 is capable of imaging, at nanoscale resolution or greater,surfaces and other substrates including individual atoms or moleculessuch as biomolecules. Device 10 can replace relevant parts (e.g., tips)of any of the above systems.

In a preferred embodiment, supporting element 18 and/or nanowire 12 maybe pre-coated with a layer of conductive material in order to produce agood electrical contact therebetween.

Device 10 is particularly useful when used in tapping mode atomic forcemicroscopy. In this mode, a change in amplitude of an oscillatingcantilever driven near its resonant frequency is monitored as nanowire12 taps the surface of nanoscale environment 14. The sharp frequencyresponse of high-quality cantilevers makes this technique exquisitelysensitive. Nanostructure 14 has the advantage that it is both stiffbelow a certain threshold force, but is compliant above that thresholdforce. More specifically, below the Euler buckling force, there is nobending of nanowire 12. The Euler buckling force of nanowire 12 ispreferably in the one nano-Newton range. Once the Euler bucking force isexceeded, nanowire 12 bends easily through large amplitudes with littleadditional force. In addition, nanowire 12 is extremely gentle whenlaterally touching an object.

The result is that gentle, reliable atomic force microscopy imaging maybe accomplished in the tapping mode with even extremely stiff,high-resonant frequency cantilevers. In contrast to the hard siliconpyramidal tip of existing systems, which can easily generate impactforces being larger than 100 nano-Newtons per tap, and therefore maysubstantially modify the geometry of soft samples such as largebio-molecules, nanowire 12 serves as a compliant probe which moderatesthe impact of each tap on the surface.

An additional advantage of device 10 is its capability to exploreregions of nanoscale environment 14 previously inaccessible to highresolution scanning probes. In this embodiment, nanowire 12 ispreferably of tubular shape so as to allow nanowire 12 to penetrate intodeep trenches of environment 14. Due to the above mention specialmechanical characteristics of nanowire 12 scanning force microscopyimaging of tortuous structures can be achieved without damaging nanowire12 or the imaged object.

Device 10 of the present invention can also be utilized to retrieveother types of information from nanoscale environment 14, such as, butnot limited to, information typically obtained via conventional frictionforce microscopy. Friction force microscopy measures the atomic scalefriction of a surface by observing the transverse deflection of acantilever mounted probe tip. The compliance of nanowire 12 above theEuler threshold as described above, provides for a totally new method ofelastic force microscopy. By calibration of the Euler buckling force fornanowire 12, and making appropriate atomic force microscopy measurementsusing nanowire 12, one can obtain direct information about the elasticproperties of the object being imaged.

Device 10 may also be used to perform nanoscale surface topographymeasurement. Motions of supporting element 18 can be calibrated bymeasurement of surfaces having known geometries (e.g., pyrolyticgraphite with surface steps). Once properly calibrated, supportingelement 18 and nanowire 12 can provide precise measurement of thetopography of surfaces and fabricated elements such as vias and trencheson integrated-circuit elements.

An additional use of device 10 is in mechanical resonance microscopy,which can be facilitated by mechanical resonances in nanowire 12. Theseresonances may be utilized as a means of transduction of informationabout the object being sensed or modified. Such resonances, as will beknown by one skilled in the art, can be sensed by optical,piezoelectric, magnetic and/or electronic means.

Nanowire 12 can also act as a sensitive antenna for electromagneticradiation. The response of nanowire 12 to electromagnetic radiation maybe recorded by detecting and measuring frequency currents passingtherethrough as it and the object being sensed interact together in anonlinear way with electromagnetic radiation of two or more frequencies.Via its interaction with electromagnetic fields of specifiedfrequencies, nanowire 12 may excite electronic, atomic, molecular orcondensed-matter states in the object being examined, and thetransduction of information about that object may occur by observationof the manifestations of these states.

Also of interest is the use of device 10 for probing biological systems.For example, device 10 can perform DNA sequencing by atomic forcemicroscopy imaging of DNA molecules whereby nanowire 12, due to itsphysical and chemical properties, permits the recognition of individualbases in the molecule. An additional apparatus for polynucleotidesequencing is further described in more details hereinafter.

In another biological application, device 10 can also be used forelectrical or electrochemical studies of living cells. Knowledge of cellactivity can be achieved, e.g., by measuring and recording electricalpotential changes occurring within a cell. For example, device 10 of thepresent invention can accurately monitor specific cytoplasmic ions andcytosolic calcium concentrations with a spatial resolution far superiorto those presently available. Living cells which can be studied usingdevice 10 include, without limitations, nerve cell bodies and tissueculture cells such as smooth muscle, cardiac, and skeletal muscle cells.

Additionally, device 10 can be used, for example, to obtain and measurenear field light from nanoscale environment 14. For the purpose ofproviding a self contained document a description of the near fieldphenomenon precedes the description of the presently preferredembodiment of the invention.

When light impinges on a boundary surface (such as the surface ofnanoscale environment 14) having a varying refractive index at an anglewhich causes total reflection, the incident light is totally reflectedon the boundary surface (reflection plane), in which case the lightexudes to the opposite side of the reflection plane. This exuding lightis called “near-field light.” Other than the foregoing, the near-fieldlight also includes light which exudes from a miniature aperture smallerthan the wavelength of the light, through which the light is passed.

The near-field light can be utilized to analyze a surface state (shape,characteristics or the like) of a sample such as semiconductormaterials, organic or inorganic materials, vital samples (cells) and thelike. An ordinary optical microscope cannot measure a sample at aresolution higher than the wavelength of light due to diffraction of thelight. This is called “diffraction limit of light.” An analysisutilizing near-field light permits measurements at a resolutionexceeding the diffraction limit of light.

According to a preferred embodiment of the present invention nanowire 12is adapted to collect near-field light of nanoscale environment 14. Asthe near-field light incidents on nanowire 12, electronic excitation areinduced therein. These electronic excitations cause a current to flowthrough nanowire 12, toward detection system 16 which detects, recordsand/or analyzes the current.

It is appreciated that the above embodiments merely exemplify thepotential use of device 10 for obtaining vital information from ananoscale environment, previously unattained by conventional systems andapparati. The geometrical shape, nanometric size and physical propertiesof nanowire 12 may also be used also for performing tasks, other than,obtaining information.

When two nanostructures encapsulating a conducting material arepositioned in closed proximity one to another, a nanometer-scale gap canbe formed. Such nanometer-scale gap, also referred to herein as ananogate, is used in the present invention as a polynucleotide detectiongate.

Thus, according to another aspect of the present invention, there isprovided an apparatus 11 for characterizing a nucleic acid sequence of apolynucleotide.

Reference is now made to FIGS. 4 a-b, which schematically illustrate atop view (FIG. 4 a) and a side view (FIG. 4 b) of apparatus 11.Apparatus 11 comprises a nanogate 13 defined by two conducting nanowires12, which, as stated, are formed of a conducting material enclosed bythe peptide nanostructures of the present invention. A typical distancebetween nanowires 12, i.e., a typical width of nanogate 13 is betweenabout 1 nm and 10 nm, inclusive more preferably between about 2 nm and 6nm, inclusive. Nanowires 12 are preferably formed on a hydrophilic andnonconductive (e.g., silicon oxide) surface 15.

Apparatus 11 further comprises a positioning device 17, for positioningthe polynucleotide 19 within nanogate 13. As further detailedhereinunder, in one embodiment, positioning device 17 comprises anarrangement of electrodes 9 designed and constructed to generate anelectric field capable of inducing electrophoresis forces onpolynucleotide 19.

A controlled thin layer of water or other liquid on surface 15facilitates the loading and delivery of polynucleotide 19 through thenanogate 13. The width of nanogate 13 (1-10 nm) is sufficient forpassage of a single polynucleotide. One ordinarily skilled in the artwould appreciate that the specific requirement for nanogate width isalso dependent on the temperature and solvent conditions such as the pHand ionic strength of the water or the liquid layer.

When the distance between nanowires 12 is within the above range,significant electron tunneling across the nanogate 13 is generated withapplication of a tunneling biased voltage thereon. In an aqueoussolution (e.g., water), the width of a single-stranded DNA molecule isabout 2-3 nm (including some bound water molecules), while that of adouble-stranded DNA is about 3-4 nm. Thus, the above preferred rangesfor the width of nanogate are sufficient for the passage of either typeof DNA chain, and for detection by tunneling current measurement.

The thickness of the adsorbed water or liquid layer increases withincreasing humidity. By controlling the relative humidity, the thicknessof the water layer can be manipulated. In addition, by using specifictypes of surfaces or chemically modified ones, the water adsorption, andthus the thickness of the water layer, can be enhanced. It is possibleto maintain a water layer with a thickness that is comparable to that ofa single- or double-stranded DNA molecule.

When a nucleic acid sample is loaded into apparatus 11 (e.g., using amicro- or nano-fluidic injection device, not shown), positioning device17 delivers polynucleotide 19 to nanogate 13, for example, by a pair ofelectrodes 9.

A precise control of the locomotion of polynucleotide 19 is achievedthrough the use of electric fields in conjunction with the water orliquid layer. According to a preferred embodiment of the presentinvention, two electric fields are generated by positioning device 17.The first such field is preferably parallel to surface 15. This field,preferably controlled by electrodes 9, is selected so as to induceelectrophoresis forces on polynucleotide 19 in a direction which isparallel to surface 15.

The second electric field is preferably perpendicular to surface 15.This field serves for holding polynucleotide 19 in place and ispreferably applied using two planar electrodes 21, located above andbeneath surface 15 (sees FIG. 4 b).

Thus, the step size of polynucleotide 19 in movement on surface 15 andthrough nanogate 13 is controlled by the direction, magnitude andduration of the parallel electric field in conjunction with theperpendicular electric field. According to a preferred embodiment of thepresent invention these two electric fields and the process of molecularcharacterization are synchronized and coordinated to minimize the timespent by polynucleotide 19 in device apparatus 11. To provide anefficient characterization process, when polynucleotide 19 entersnanogate 13 the parallel electric field is preferably temporarilyterminated until the characterization process is completed.

With the perpendicular electric field at the proper magnitude anddirection, polynucleotide 19 remains in its location in nanogate 13. Forexample, for a single-stranded DNA molecule, the perpendicular electricfield is preferably directed upwards, so that the (negatively charged)phosphate groups of the DNA molecule are pulled down on surface 15,while its nucleotides pointing upward as desired for base detection. Anadditional advantage of the use of perpendicular electric field is thatthis filed prevents any potential drift polynucleotide 19.

When the characterization process is completed, the parallel electricfield is generated again so as to remove polynucleotide 19 from gate 13and to guide another polynucleotide into gate 13.

The characterization process of polynucleotide 19 using nanogate 13 isknown in the art (to this end see, e.g., U.S. Patent Application20030141189, the contents of which are hereby incorporated byreference). For example, one method is by measuring tunneling currentacross nanogate 13. Since the chemical compositions and structures ofthe nucleotides are different, the screening effect of each distinctnucleotide on the tunneling current and other tunneling parameters isdifferent. Representative examples of tunneling parameters, beside thetunneling current, include, without limitation, tunneling I-V curveand/or tunneling dI/dV-V curve, where I represent the tunneling currentV represent the tunneling voltage and dI/dV represent the tunnelingcurrent slope (first derivative).

Thus, by detecting the difference in the tunneling parameterspolynucleotide passing through nanogate 13, the nucleic acid sequence ofthe polynucleotide can be determined. Using some DNA molecules of knownsequence, apparatus 11 can be calibrated, so as to establish a uniquetunneling characteristic profile for each distinct DNA base. Thistunneling profile is then used as a fingerprint to identify anindividual base. With the ability to move polynucleotide 19 throughnanogate 13 in a well-controlled manner, reliable sequence informationcan therefore be obtained at a speed much faster than the current DNAsequencing technology. Since the tunneling electrons likely emerge froma single (or a few) atom(s) of one nanowire, and tunnel through thenanogate 13 to the tip of the other nanowire for the shortest possibledistance, the size of the tunneling electron beam is likely to be withina few angstroms (a fraction of a nanometer). This is sufficiently fineto make precise detection of an individual nucleotide of the DNAmolecule possible. Therefore, the tunneling detection method can offer abetter resolution than that of atomic force microscopy (AFM) probing,described below. The tunneling current method should be able to performDNA sequencing on either single-stranded or double-stranded DNAmolecules.

Other methods of nucleic acid sequence characterization which arecontemplated are, dielectric constant measurements, atomic forcemicroscopy (AFM) or electrostatic force microscopy (EFM) probing.

When the tips of nanowires 12 are placed in close proximity to eachother, they can act as elements of a parallel plate capacitor. Analternating voltage (AC voltage) applied between the nanowires 12 incharacterized by a phase lag of 90° between the applied voltage andmeasured current. When a dielectric material such as a nucleic acidmolecule is present between the nanowires, the phase lag varies as afunction of the dielectric constant of the dielectric material. Thus,according to a preferred embodiment of the present invention, thenucleic acid sequence characterization is done by measuring thedielectric constant of polynucleotide.

The capacitance of the parallel plate capacitor depends on thedielectric constant of the nucleotides and the liquid that are betweennanowires 12. For example, the four DNA nucleotides (thymine, adenine,cytosine and guanine) have different structures and compositions, hencealso different dielectric constants. When the DNA molecule is positionedin water, the interaction between the DNA and the water molecules alsocontributes to differences in dielectric constant. Some water moleculesare bound or semi-bound around the DNA chain thus less freedom forrotation and are thus less polarizable than the free water molecules ina bulky phase. Consequently, the dielectric constant of the bound orsemi-bound water molecules is significantly smaller than that of freewater molecules. Since each of the nucleotides has a somewhat differentorientation and spatial relation with the phosphate chain, the geometryof the bound or semi-bound water molecules around each distinctnucleotide is also somewhat distinct. This distinct geometry can conferdifferent dielectric constants for each base.

The dielectric constant can be determined by measuring by measuring thephase shift between the input AC voltage and an output voltage signal.Knowing the phase shift, the input and output voltages and the ACfrequency, the capacitance, hence also the dielectric constant ofpolynucleotide 19 can be determined.

By using some DNA molecules of known sequence, calibration of thedielectric constant measurement is possible. A unique phase-shiftprofile can be established for each distinct DNA base. This profile canbe used as a fingerprint to identify an individual base.

Nanostructure generated in accordance with the teachings of the presentinvention can also be utilized as part of a field emitting device.

Hence, according to another aspect of the present invention, there isprovided a field emitter device, which is referred to herein as device20.

Reference is now made to FIG. 5 a, which is a schematic illustration ofa cross sectional view of device 20, according to a preferred embodimentof the present invention. Device 20 preferably comprises an electrode 22and a nanowire 12. Electrode 22 and nanowire 12 are designed andconstructed such that when an electrical field is formed therebetween,electrons 27 are extracted from nanowire 12 by tunneling through thesurface potential barrier. Once emitted from nanowire 12, electrons 27can be accelerated, redirected and focused so as to energetically exciteatoms of a specific material, as further detailed hereinunder.

Device 20 may be integrated in many apparati, such as, but not limitedto, a field emitter display. In this embodiment, a plurality ofnanostructures may be positioned in cross points 28 of a matrix 29 ofelectrodes. Matrix 29, better illustrated in FIG. 5 b, is formed of aplurality of row and column electrodes. Thus, each cross point 28 can beaddressed by signaling the respective row and column electrodes. Upon asuitable signal, addressed to a specific cross point, the respectivebundle of nanostructures 12 emits electrons, in accordance with theabove principle.

Device 20 (or the apparatus in which device 20 is employed) may furthercomprise a substrate 26 having a fluorescent powder coating, capable ofemitting light upon activation by the electrons. The fluorescent powdercoating may be either monochromatic or multichromatic. Multichromaticfluorescent powder may be, for example, such that is capable of emittingred, green and blue light, so that the combination of these colorsprovides the viewer with a color image. Device 20 may further comprise afocusing element 25 for ensuring that electrons 27 strike electrode 22at a predetermined location.

A special use of field emitter device, such as device 20, is in the areaof electron beam lithography, in particular when it is desired toachieve a precise critical dimension of order of a few tens ofnanometers. The present invention successfully provides an apparatus forelectron emission lithography apparatus, generally referred to herein asapparatus 30. As further detailed hereinbelow, apparatus 30 is capableof transferring a pattern of a mask in a nanoscale resolution.

Reference is now made to FIG. 6, which is a schematic illustration ofapparatus 30. Apparatus 30 comprises an electron emission source 32 andan electrically conducting mounting device 34. According to a preferredembodiment of the present invention, sources 32 includes one or morenanostructures 12, which, as stated, is composed of a plurality ofpeptides. Source 32 and mounting device 34 are kept at a potentialdifference, e.g., via a voltage source 36. The potential difference isselected such that electrons are emitted from source 32 (similarly todevice 20).

A sample 38, on which an e-beam resist 39 to be patterned is formed, isdisposed on mounting device 34, in a predetermined distance apart from asource 32. The electrons emitted from nanowire 12 perform a lithographyprocess on a sample 38 mounted thereon. Subsequently, if a developingprocess is performed, portions of resist 39 which were exposed to theemitted electrons remain when the resist 39 is negative, while portionsof resist 39 not exposed to an electron beam remain when resist 39 ispositive.

Source 32 and mounting device 34 are preferably positioned in a magneticfield generated by a magnetic field generator 37. Magnetic fieldgenerator 37 is designed to precisely control a magnetic field accordingto the distance between nanostructures 12 and resist 39, so that theelectrons emitted from nanowire 12 reach the desired positions on resist39. Being charged particles moving in a magnetic field, the electronsare subjected to a magnetic force, perpendicular to their direction ofmotion (and to the direction of the magnetic field vector). Thus, atrack of the movement of the electrons is controlled by magnetic fieldgenerator 37, which redirect the electron to the desirable position.

Consequently, the shape of nanostructures 12 can be projected uponsample 38, to thereby perform a lithographic process thereon. Asdescribed above, according to the present invention, sincenanostructures 12 are used as electron emission sources, a lithographyprocess can be performed with a precise critical dimension. In addition,since electrons emitted from nanostructures 12 carbon depreciateportions of resist 39 corresponding to nanowire 12, a deviation betweenthe center of a substrate and the edge thereof are substantiallyprevented.

An additional use of nanowire 12 is in the field of information storageand retrieving. In certain embodiments, further detailed hereinunder,switching may be achieved based on the observation that the conductanceof semiconducting nanowires can change significantly upon either a gateor bias voltage pulse when the surface of the nanowires areappropriately modified, for example, with molecules, functional groupsor nanocrystals. Other properties of the nanowire may also be used torecord memory, for example, but not limited to, the redox state of thenanowire, mechanical changes, magnetic changes, induction from a nearbyfield source, and the like.

Specifically, with respect to changes in conductance, subjection topositive or negative gate or bias voltage pulses may cause the change ofcharge states in the molecules or nanocrystals, and induces the deviceto make a fully reversible transition between low and high resistancestates. The different states may hysterically persist in the set state,even after the voltage source is deactivated. This feature (change inelectrical properties upon voltage pulse) may enable the fabrication ofelectrically erasable and rewritable memory switching devices in whichthe reversible states are indicated by the conductance of the nanowires.In addition, the memory switching devices may be assembled specificallyfrom nanoscale material building blocks, and may not be created inplanar materials by lithography.

Reference is now made to FIGS. 7 a-b, which are schematic illustrationof a memory cell, generally referred to herein as cell 40. In itssimplest configuration, cell 40 comprises an electrode 42 and a nanowire12. Nanowire 12 preferably capable of assuming one of at least twostates. For example, as already described hereinabove, nanowire 12 hasthe capability to deflect when the Euler buckling force is exceeded,thus, a first state of nanowire 12 can be a non-deflected state (when anexternal force applied on nanostructure is below Euler buckling force)and a second state of nanowire 12 can be a deflected state (when theexternal force is above or equals the Euler buckling force).

Nanowire 12 is preferably be suspended by one or more supports 44 overelectrode 42. Nanowire 12 may be held in position on support(s) 44 inmore than one way. For example, nanowire 12 is held in position onsupport(s) 44 by or any other means, such as, but not limited to, byanchoring nanowire 12 to support(s) 44. The holding of nanowire 12 inits place on support(s) 44 can also be facilitated by chemicalinteractions between nanowire 12 and support(s) 44, including, withoutlimitation, covalent bonding.

Electrode 42, nanowire 12 and the distance therebetween are preferablyselected such that electrical current flows through electrode 42 and/ornanowire 12, generates an electric force on nanowire 12 which is largerthan the Euler buckling force. Thus, temporarily electric current(s)transform nanowire 12 from the first state (FIG. 7 a) to the secondstate (FIG. 7 b).

A plurality of cells like cell 40 can be incorporated to provide anelectromechanical memory array. Each cell in the array can be in eithera first state or a second state thus can store a binary information of afirst type of datum (say, “0”) and a second type of datum (say, “1”). Asthe size of nanowire 12 is in the nanometric scale, many such cells canbe integrated in a single array so that the information storage capacityof the entire array is substantially larger, or at least equivalent tomodern memory devices. Each cell may be read or written by applyingcurrents and or voltages to electrode 42 or nanowire 12.

More specifically, when nanowire 12 is in a non-deflected state (FIG. 7a), cell 40 is characterized by an open circuit, which may be sensed assuch on either nanowire 12 or trace electrode 42 when so addressed. Whennanowire 12 is in a deflected state (FIG. 7 b), cell 40 is characterizedby a rectified junction (e.g., Schottky or PN), which may be sensed assuch on either nanowire 12 or trace electrode 42 when so addressed.

As will be appreciated by one ordinarily skilled in the art, cell 40(and therefore an integrated array of a plurality of such cells) ischaracterized by a high ratio of resistance between “0” and “1” states.Switching between these states is accomplished by the application ofspecific voltages across nanowire 12 or electrode 42. For example,“readout current” can be applied so that the voltage across a respectivejunction is determined with a “sense amplifier.” It will be appreciatedthat such reads are non-destructive. More specifically, unlike DRAMsystems, where write-back operations are required after each read, cell40 retains its state even once read is performed.

As stated, the nanostructure of the present invention can alsoencapsulate a magnetic material, hence to form a magnetic nanowire. Aplurality of such magnetic nanowires can be used as a memory cell, whichoperates according to magnetic principles.

Reference is now made to FIG. 8, which is a schematic illustration of amemory cell, generally referred to herein as cell 60. Cell 60 comprisesa plurality of nanowires 12, each formed of a ferromagnetic materialenclosed by a peptide nanostructure, as further detailed herein above.Nanowires 12 are capable of assuming two magnetization states. Onemagnetization state (designated M₁ in FIG. 8) may be defined, forexample, when the magnetization vector, M, is substantially parallel toa longitudinal axis 62 of nanowires 12 and another magnetization state(designated M₂ in FIG. 8) may be when the magnetization vector has anon-negligible angle (say, above 10°) with respect to axis 62.

Thus, binary information can be stored by the two magnetization statesof nanowires 12. For example, state M₁ can be defined as “0” and stateM₂ can be defined as “1”. One ordinarily skilled in the art wouldappreciate that well separated magnetization states, also known as amagnetization jump, can be obtained and reproduced precisely from onenanowire to the other by working with nanowires of ferromagneticmaterials. The jump from one magnetization state to the other ispreferably identified by sweeping an external magnetic field, so thatwhen its magnitude is below a proper threshold, characteristic to theferromagnetic material and structure of nanowires 12, nanowires 12assumes the first magnetization state and when the magnitude of theexternal magnetic field magnitude is above the characteristic threshold,nanowires 12 assumes the second magnetization state.

Cell 60 further comprises a plurality of conductive lines 63, preferablyarranged on opposite sides of a membrane 65, such that each nanowire ofplurality of nanowires 12 is connected to two conductive lines ofplurality of conductive lines 63. This allows for a unique address,represented by a pair of gridwise numbers, to be assigned to eachindividual nanowire. For example, referring to FIG. 8, nanowire 12 a,which is connected to conductive lines 63 i and 63 j is represented bythe address (63 i, 63 j).

The operation of cell 60 is based upon a physical effect known as theanisotropic magnetoresistance effect, according to which a component ofthe electrical resistance of a magnetic element varies with a change inthe magnetization orientation of the element and the sensing currentflowing therethrough. The change in the electrical resistance depends onthe angle between the magnetization vector and the electrical current.

Specific methods of writing and reading information into and out of cell60 can be found, for example, in U.S. Pat. No. 6,172,902 the contents ofwhich are hereby incorporated by reference.

Generally, the writing processes to a given address, say, address (63 i,63 j), is preferably done by injecting a pulsed current into therespective pair of conductive lines, when the magnitude of the externalmagnetic field is lower by an amount of ΔH than the characteristicthreshold H_(s). The result of the pulse is to induce the jump from themagnetic state “0” to state “1”. The reading process at a given addressis preferably done by injecting a current and measuring the potentialbetween the respective pair of conductive lines at a value of theexternal magnetic field which is between H_(s)−ΔH and H_(s). Due to themagnetoresistive property of nanowire 12, the value of the electricpotential is shifted.

According to another aspect of the present invention, there is providedan electronic device, for switching, inverting or amplifying, generallyreferred to as device 50.

Reference is now made to FIG. 9 a, which is a schematic illustration ofdevice 50. Device 50 comprises a source electrode 52, a drain electrode54, a gate electrode 56 and a channel 58. One or both of gate electrode56 and channel 58 may be formed of a semiconducting material enclosed bya nanostructure which is composed of a plurality of peptides, as furtherdetailed hereinabove. For example, in one embodiment channel 58 is ananostructure and gate electrode 56 is preferably layer of SiO₂ in asilicon wafer.

In its simplest principle, device 50 operates as a transistor. Channel58 has semiconducting properties (either n-type or p-type semiconductingproperties) such that the density of charge carriers can be varied. Avoltage 57 is applied to channel 58 through gate electrode 56, which ispreferably separated from channel 58 by an insulating layer 59. When thevoltage of gate electrode 56 is zero, channel 58 does not contain anyfree charge carriers and is essentially an insulator. As voltage 57 isincreased, the electric field caused thereby attracts electrons (or moregenerally, charge carriers) from source electrode 52 and drain electrode54, so that channel 58 becomes conducting.

Thus, device 50 serves as an amplifier or a switching device where,voltage 57 of gate electrode 56 controls the current flowing from sourceelectrode 52 and drain electrode 54, when a bias voltage 53 is appliedtherebetween.

Two devices like devices 50 may be combined so as to construct aninverter. Referring to FIG. 9 b, in this embodiment, a first such device(designated 50 a) may include a channel having an n-type semiconductingproperties and a second such device (designated 50 b) may include achannel having an p-type semiconducting properties. Devices 50 a and 50b are preferably connected such that when bias voltage 53 is appliedbetween the source of device 50 a and the drain of device 50 b, thecombined device serves as an inverter between input signal 51 and outputsignal 55.

An additional configuration which includes semiconducting nanowire isillustrated in FIG. 10 a. In this embodiment, two nanowires 12 forming ajunction 92 can serve as a transistor 90. Preferably, the semiconductingmaterial of one of the two nanowires has an n-type doping and thesemiconducting material of the other nanowire has a p-type doping.

In accordance with the present invention, one or both of nanowires 12 oftransistor 90, has a modulation-doped semiconductor material. This maybe achieved by providing a nanowire having either Lewis acid functionalgroups or Lewis base functional groups to create a region of modulationdoping in the junction. One of nanowires 12 comprises the source and thedrain portions of transistor 90 and the other nanowire induces the gatefunction at junction 92. Both pnp and npn transistors that are analogousto bipolar transistors may be formed in this fashion.

Several junctions like junction 92 can be allocated to form a crossbararray 94, which can be used for signal routing and communicationsbetween two layers of nanowires. According to the presently preferredembodiment of the invention crossbar array 94 comprises atwo-dimensional array of a plurality of junctions similar to junction92. Each junction servers as a switch which can be either singlyconfigurable or reconfigurable and self-assembling. In one embodiment,at least one of the junctions is a quantum state molecular switch havingan electrically adjustable tunnel junction between the respective twonanowires. The switches, formed at each junction, can beelectrochemically oxidized or reduced. Oxidation or reduction of themolecule forms the basis of a switch. Oxidation or reduction affects thetunneling distance or the tunneling barrier height between the twonanowires, thereby exponentially altering the rate of charge transportacross the junction.

Reference is now made to FIG. 10 b which is a simplified illustration ofarray 94. Array 94 comprises a plurality of junctions 92 defined whentwo nanowires 12 are crossed at some non-zero angle. Nanowires 12 can beformed of a conducting or semiconducting material enclosed by a peptidenanotube, as further detailed hereinabove. When an appropriate voltageis applied across the nanowires, molecules of each of the two nanowiresat the junction point are either oxidized or reduced. When a molecule ofone nanowire is oxidized, then a molecule of the other nanowire isreduced so that charge is balanced. These two species are referred toherein as a redox pair.

Distinct electrical circuits 96 a and 96 b and 96 c may be created inarray 94 as part of an integrated circuit. Circuits 96 a, 96 b and 96 ccan cross each other without being electrically connected whereswitches, shown as open circles in FIG. 10 b and designated 98 a, areopen. Alternatively, nanowires may be electrically connected by a closedswitch, shown as a filled circle in FIG. 10 b and designated 98 b. Byusing the voltage across the electrochemical cell formed by each pair ofcrossed nanowires to make and break electrical connections both alongnanowires in a layer (segmented wires) and between wires in two layers(vias), one can create an integrated circuit of arbitrarily complextopology. The wires may connect to an external or an internal electronicdevice (not shown), e.g., a resonant tunneling diode or a transistor.

This freedom to select a mixture of device types and interconnecttopologies includes the possibility that nanowires 12 are heterogeneousin their composition or functionalization. The nanowires in a givenlayer can be separately formed and functionalized in a plurality ofdifferent ways, and subsequently assembled to form a layer that isheterogeneous in nanowire type.

The conducting nanowires of the present invention can also serve asconducting interconnects for electronic circuit assembly of multiplelayers. Multi-layered electronic assemblies are used to interconnect alarge number of circuit layers. A typical multi-layered assembly hasseveral layers of signal lines, separated by interleaving dielectriclayers, and via connections running through one or more dielectriclayers perpendicular to the layers surface, as required by the specificelectric interconnect network of the assembly.

Reference is now made to FIG. 11, which is a simplified illustration ofan electronic circuit assembly 100, according to a preferred embodimentof the present invention. Assembly 100 comprises conductive lines 102being arranged in at least two layers 104 separated therebetween by adielectric layer 106. Several conductive lines 102 are electricallyconnected via one or more conductive nanowire 12. Nanowires 12preferably serve as passive conductors for facilitating electricalcommunication between different layers of assembly 100.

As used herein, the phrase passive conductor referrers to a conductorcapable solely to transmit electrical current therethrough.

As used herein, the phrase dynamical conductor referrers to a conductorcapable of having to states: a transmissive state in which the conductorserve as a passive conductor and a non-transmissive state in which noelectrical current is transmitted therethrough.

It will be appreciated that assembly 100 can be combined also with array94 or several elements thereof, so that nanowires 12 can also be useddynamically. For example, some nanowire can serve mealy as verticallyconductive lines between different layers (passive conductors), whileother nanowires may form one or more junctions, similar to junction 92,thus allowing switching (dynamic conductors) as further detailedhereinabove.

An additional application in which the nanowires of the presentinvention can used is in a device for detecting a position and/ormovement of an object. Position sensors are used in a variety of moderndevices and transducers, for example, in applications for robotics andcomputer hardware. In robotics, such sensors provide useful informationabout the state of contact between a robot hand and an object inprehension. In computer-related products such sensors are employed indevice such as, but not limited to, mouse, joystick and the like, whichrespond to movement in two dimensions.

Reference is now made to FIG. 12 a, which is a simplified illustrationof a device for detecting a position and/or movement of an object,generally referred to herein as device 120. Device 120 comprises aplurality of non-intersecting nanowires 12, formed of conducting ormagnetic material enclosed by the peptide nanostructure of the presentinvention. Nanowires 12 are connected to an electronic circuitry 122,which may have a flat surface or a macroscopically non-flat surface,e.g., a robot's finger tips. The connection between nanowires 12 andcircuitry 122 may be via an array of contact pads 124. Each contact padmay be allocated with more than one nanowire so as to form a bundle ofnanowires.

FIG. 12 b is a schematic illustration of device 120 when contacted by anobject 126. Three nanowires are shown in FIG. 12 b, designated 12 a, 12b and 12 c. In operational mode, object 126 contacts nanowire 12 a andelastically bends it so that nanowire 12 a intersects nanowire 12 bwhich is adjacent thereto. An electrical connection 128 between nanowire12 a and nanowire 12 b is thus made possible. Similarly, when objects126 continues to move, other intersections occur (e.g., betweennanowires 12 b and 12 c).

The location at which object 126 contacts device 120 can thus bedetected based on the criterion of electrical connection/no-connectionbetween pairs of contact pads. Device 120 is capable of detecting theposition, area, direction of movement, and intensity or strength of thetactile contact (the contact of object 126 with device 120). Thesefactors are generally referred to herein as the position and movementactivity of object 126. The position and movement activity can beevaluated by interrogating pairs of contact pads to determine whether anelectrical connection has been made between adjacent nanowires.

Whether a connection between nanowires 12 has been made can be sensed bysending a current pulse to contact pads 124 and measuring the electricalresistance. The location of the object can be determined quantitativelybased on the number of nanowire being electrically connected at anymoment. The time sequence at which the electrical connections areeffected provides information on the direction of the motion of object126. Contact pads 124 can be interrogated sequentially or simultaneouslyto detect the electrical connection.

The intensity of the tactile force on device 120 may be determined invarious ways, such as, but not limited to, evaluation of the physicalcontact resistance between nanowires that are bent and in contact. Thevalue of the electrical resistance between connected depends on theforce applied on nanowire 12.

The conducting or semiconducting nanowires of the present invention mayalso be used in the field of electrophoretic displays. As stated in thebackground section that follows, electrophoretic displays employ aplurality of electrically charged particles suspended in a fluid. Underthe influence of electric field, the charged particles move through thefluid hence locally alter the optical characteristics of the display.

According to an additional aspect of the present invention there isprovided a display system, generally referred to herein as system 130.

Reference is now made to FIG. 13 which is a schematic illustration ofsystem 130. System 130 comprises a fluid 132 containing a plurality ofnanostructure devices 134, each being formed of a conducting orsemiconducting material enclosed by a peptide nanostructure, as furtherdetailed hereinabove.

Nanostructure devices 134 are distinguished from the pigment particlesused in prior art electrophoretic displays by their size. Pigmentparticles are typically of the order of several hundred nanometers indiameter, or larger. Thus, the diameters of even the smaller pigmentparticles are of the same order as the wavelengths of visible light,which vary from about 400 nm for blue light to about 700 nm for redlight. It is well known to those skilled in the art that the lightscattering power of particles is approximately proportional to the sixthpower of the particle diameter for particles having diameters less thanthe wavelength of the relevant light.

Thus, isolated nanostructure devices, which are much smaller than thetypical wavelength of light do not appreciably scatter the light and, assuch, are effectively transparent. However, the nanostructure devices,when brought into proximity with one another and thus aggregated intolarger clusters having diameters comparable to the wavelength of light,scatter light strongly. Thus, by controlling the aggregation level ofnanostructure devices 134, one can determine whether the nanostructuredevices 134 appear transparent or turbid.

System 130 further comprises an electric field generator 136 capable ofgenerating an electric field effective in shifting nanostructure devices134 between a dispersed state, corresponding to a first opticalcharacteristic and an aggregated state corresponding to a second opticalcharacteristic.

Conducting nanostructure devices, such as peptide nanostructureencapsulating silver or gold, change color with aggregation. This colorchange is due to the change in the average refractive index as theaggregates form. When conducting nanostructure devices aggregate, boththe color and the intensity of light scattering increases. In otherwords, the first and second optical characteristics of the displaysystem comprise different colors. For example dispersions of goldnanostructure devices are typically ruby red, while aggregates of goldnanostructure devices vary in color from purple to blue to blackdepending on the interparticle distance. Thus, in this embodiment, thecolor of system 130 can be controlled by controlling the degree ofaggregation of nanostructure devices 134.

Semiconducting nanostructure devices have strong particle size dependentcolors in both the dispersed and aggregated states. The colors are bestand most easily seen in fluorescence, and are due to the size dependentquantization of electronic levels in nanostructure devices 134. Thesmaller the nanostructure device, the larger the band gap and theshorter the wavelength of the fluorescence. Semiconducting nanostructuredevices have fluorescent peaks that vary smoothly from about 400 nm toabout 700 nm (red) when the size of the nanostructure device varies fromabout 1.2 nm to about 11.5 nm.

An additional application in which the peptide nanostructures of thepresent invention can be useful is in the field of thermoelectricity.Thermoelectric devices are devices that either convert heat directlyinto electricity or transform electrical energy into pumped thermalpower for heating or cooling. Such devices are based on thermoelectriceffects involving relations between the flow of heat and of electricitythrough solid bodies.

The formulation of the thermoelectric effect, also known as the Seebeckeffect, is as follows. When an open circuit made of a pair of dissimilarmetals is held so that two junctions are kept at different temperatures,a potential difference is produced across the terminals of the opencircuit. The potential difference is directly proportional to thetemperature difference, and does not depend on the distribution oftemperature along the metals between the junctions. The factor ofproportionality, referred to in the literature as the relative Seebeckcoefficient, generally varies with the level of the temperature at whichthe temperature difference occurs.

The flip side of the Seebeck effect is known as the Peltier effect.According to the Peltier effect a current driven in a circuit made ofdissimilar metals causes the different metals to be at differenttemperatures. Depending on the direction of current flow, heat could beeither removed from a junction to freeze water into ice, or by reversingthe current heat can be generated to melt ice. The heat absorbed orcreated at the junction is proportional to the electrical current, andthe proportionality constant is known as the Peltier coefficient. ThePeltier effect is caused by the fact that an electrical current isaccompanied by a heat current in a homogeneous conductor even atconstant temperature. The heat current is interchangeably referred toherein as power, as the two quantities have the same physical dimensions(energy per unit time).

The heat current accompanying the electric current, I, is explained bythe different flow velocities of the electrons carrying the electriccurrent. The flow velocities depend on the energies of the conductionelectrons. For example, if the flow velocity of electrons having anenergy above the Fermi energy is higher than for electrons with a lowerenergy, the electric current is accompanied by a heat current in theopposite direction (since the electronic charge is negative). In thiscase the Peltier coefficient is negative. Similar situation occurs in ann-doped semiconductor where the electric current is carried by electronsin conduction-band states. Opposite situation (i.e., electrical and heatcurrents flowing in parallel direction) occurs for a p-dopedsemiconductor where the electric current is carried by holes.

The operation of thermoelectric devices is based on the Peltier effect.Generally, thermoelectric devices have thermoelectric materialssandwiched between ceramic plates. When the plates have differenttemperatures (due to the current flowing therebetween) and the heat atthe hot plate is dissipated to the ambient environment, this assemblybecomes a cooling unit.

Besides the pumping of heat away from the cold plate, there exists twoadditional thermal processes, which conflict with the Peltier cooling:Joule heating, originating from the electromotive source generating theelectrical current, and heat conduction current, flowing from high tolow temperatures. The coefficient-of-performance of the cold plate of athermoelectric device is defined as the ratio of the power at the coldplate, to the total power of the device. The figure-of-merit of thethermoelectric device is defined as S²σT/κ, where S is the Seebeckcoefficient, σ is the electrical conductivity, T is the temperature andκ is the thermal conductivity of the device. An efficient thermoelectricdevice is characterized by high coefficient-of-performance and highfigure-of-merit.

As the Seebeck coefficient, S, and the electrical conductivity, σ, arecompeting quantities, any attempt to increase the Seebeck coefficient,results in a decrement of the electrical conductivity. It is thereforeappreciated that in conventional materials, a limit to thefigure-of-merit is rapidly obtained. Moreover, for a giventhermoelectric device, designed for a specific application at a specificrange of temperatures, the power of the cold plate and thecoefficient-of-performance reach their maximal values at differentcurrents. Practically in conventional thermoelectric devices the currentis compromisingly selected in the range between the maximum efficiencyand the maximum cooling power.

Hence, the temperature difference between the hot and the cold platesimposes severe limitations on the efficiency of the device. Moreover,even for low temperature differences, in many applications, especiallyfor cooling of small areas, conventional thermoelectric devices are notcapable of pumping the required heat fluxes.

The use of low dimensions in the design of thermoelectric devices, isknown to have several advantages: (i) enhanced density of states, due toquantum confinement effects, results in an endearment of the Seebeckcoefficient without a reduction in the electrical conductivity; and (ii)boundary scattering of electrons or holes reduces the thermalconductivity more than the electrical conductivity, hence furtherincreases the figure-of-merit.

Being practically a one dimension object, the peptide nanostructure ofthe present invention can be employed in thermoelectric devices. Thethermoelectric devices of the present invention can be used in numerousareas of applications, such as, but not limited to, military, medical,industrial, consumer, scientific/laboratory, electro-optics, computersand telecommunications areas. For example, in communications systems,the thermoelectric devices of the present invention can be used keeppower amplifiers of transceivers at operating temperature. In the areaof laser devices and, more particularly, semiconductor laser devices,the thermoelectric devices of the present invention can be used fortransporting heat away from small areas, thereby to control theoperating temperature of the semiconducting laser device. Additionally,the thermoelectric devices of the present invention can be used tostabilize temperature in multiplexed fiberoptics communications systems,where heat generation and thermal management is becoming one of thebarriers to further increase clock speeds and decrease feature sizes.Still in addition, the thermoelectric devices of the present inventioncan be used in microprocessors and digital signal processors, where avery small area of high heat must be removed quickly and efficiently.

Thus, according to a yet additional aspect of the present invention,there is provided a thermoelectric device 140.

Reference is now made to FIG. 14 which is a schematic illustration ofdevice 140. Device 140 comprises a first heat conducting layer 142 and asecond heat conducting layer 144, where first 142 and second 144 heatconducting layers are interposed by a plurality of nanowires 12.Nanowires 12 are formed of a thermoelectric material encapsulated by thepeptide nanostructure of the present invention, as further detailedhereinabove.

It is recognized that the efficiency of thermoelectric device 140 isincreased by decreasing the leg diameter to a size at which quantumconfinement effects occur. Thus, by using nanowires 12 of the presentinvention, the performance efficiency is substantially increased. Morespecifically, because the charge carrier mobility in nanowires 12 isenhances due to quantum confinement effects present therein, the Seebeckcoefficient is increased substantially without a decrease in theconductivity of the device.

According to a preferred embodiment of the present invention there aretwo branches of nanowires 12, designated 12 a and 12 b in FIG. 14.Nanowires 12 a are connected to layer 142 through an electricallyconductive layer 146 and nanowires 12 b are connected to layer 142through an electrically conductive layer 148. Layer 144 is preferablyelectrically conductive. Layers 146 and 148 have no electricalcommunication thereamongst, other than the electrical communicationthrough nanowires 12 a, nanowires 12 b and layer 144. Nanowires 12 a and12 b preferably have opposite doping nature. For example nanowires 12 amay be p-type semiconductors and nanowires 12 b may be n-typesemiconductors or vice versa.

When current flows from an electromotive source (not shown), freeelectrons flow through nanowires 12 b from layer 142 to layer 144, andholes flow through nanowires 12 a from layer 144 to layer 142. In thefollowing, the operation of the 12 b branch of device 140 will beexplained. One ordinarily skilled in the art would appreciate that asimilar description applies also for the second branch, by reversing thesign of the heat and charge carriers, i.e., by replacing electrons withholes.

In operative mode, layer 142 absorbs heat from the environment. Theresulting effect is a heat current flowing anti-parallel to theelectrical current generated by the electromotive source. In otherwords, the heat (or a portion thereof) is carried by the electronsflowing through nanowires 12 b in the direction of plate 144. During thetransition of electrons from plate 142 to nanowire 12 b, the electronsreceive additional energy, sufficient for moving from the Fermi level offree electrons in plate 142 to the conduction band in nanowires 12 b.This energy is taken from layer 142 by annihilating phonons in itslattice. Thus, energy is pumped away from layer 142.

When the electrons of nanowires 12 b arrive to layer 144, their kineticenergy is delivered thereto, for example, by producing phonons. Thus,energy, originated from layer 142 is transferred to layer 144.Subsequently, the heat is dissipated to the environment, for examplewith the aid of a heat sink.

Reference is now made to FIG. 15, which is a schematic illustration ofanother thermoelectric device, generally referred to herein as device150. According to a preferred embodiment of the present invention device150 comprises several three heat conducting regions. Shown in FIG. 15are three such regions, designated by numerals 151, 152 and 153. Device150 further comprises two semiconducting regions 154 and 155, which areconnected to regions 151, 152 and 153 via two or more nanowires 12.Nanowires 12 are formed of a conducting or thermoelectric materialenclosed by the peptide nanostructure of the present invention, asfurther detailed hereinabove.

Regions 151 and 153 are connected to electromotive sources (not shown),and provide current through device 150. Semiconducting regions 154 and155 have opposite doping nature. For example region 154 may be a p-typesemiconductor and region 155 may be an n-type semiconductor or viceversa. Region 152 serves as the cold part of device 150, while regions151 and 153 serve as the hot parts thereof. When current passes fromregion 151 to region 153 though regions 154 and 155 and throughnanowires 12, the Peltier effect causes heat to be transmitted out ofregion 152. Nanowires 12, connecting semiconducting regions 154 and 155to cold region 152, form quantum cold points. These cold points provideelectron confinement and also phonon discontinuity, which limitsvibrational energy transfer via the lattice of the materials and hencelimits heat transfer from regions 154 and 155 to cold region 152. Theseeffects improve cooling efficiency of the thermoelectric cooling device.

It will be appreciated that the elements of device 150 can, inprinciple, engage a single plane. In other words, all the components ofdevice 150 can be formed in a lateral orientation, at the same relativeheight above the substrate onto which they are formed. Such a lateralconfiguration is easier to fabricate than a top down structure informing the points because the shape can be precisely controlled.

One of the advantages of the present invention is that the principles ofdevices 140 or 150 may be exploited for many applications. For example,several thermoelectric devices may be arranged to form a thermoelectricsystem capable of pumping more heat than a single device. Beingpreferably small sized, many thermoelectric devices can be efficientlypacked into a relatively compact thermoelectric system. In addition, oneor more thermoelectric devices (e.g., a thermoelectric system) may beintegrated on an object, such as, but not limited to, an electronicchip, so as to facilitate heat release therefrom.

According to yet an additional aspect of the present invention, nanowire12 can also be used for performing mechanical tasks. For example,nanowire 12 can be used for manipulating nanoscale objects. Onepotential application of the present aspect of the invention is in thearea of assembling nanoelectronic circuit (see, e.g., cell 40, cell 60,device 50 and transistor 90 hereinabove) when nanoscale objects are tobe precisely located in a predetermined location.

Reference is now made to FIG. 16 which is a schematic illustration of ananoscale mechanical device 70, which comprises at least one nanowire 12designed and configured for grabbing and/or manipulating a nanoscaleobject 74. Nanowire 12 is formed of a conducting material enclosed bythe peptide nanostructure of the present invention, as further detailedhereinabove. The operation of device 70 may be achieved, for example,using two nanowires 12, preferably tubular nanowires, mounted on amounting device 72, whereby nanowires 12 perform a constrained motion tograb object 74.

Mounting device 72 can be, for example, a tip end of an atomic forcemicroscopy cantilever, so that one or both of nanowires 12 can also beutilized as an atomic force microscopy probe. In use, nanowires 12 firstscan (e.g., as an atomic force microscopy probe) the region where object74 is expected, thus confirming the position and shape thereof. Thisscan may be performed in any method known in the art, such as, but notlimited to, using a three-dimensional driving mechanism 78.

The motion of nanowire 12 may be controlled, for example, by a voltagesource 76 which generates an electrostatic force between nanowires 12.Thus, by activating voltage source 76 nanowires 12 can close or open onobject 74.

Once nanowire 12 grip object 74, which, as stated, has been marked bythe atomic force microscopy procedure, mounting device 72 can be movedby three-dimensional driving mechanism 78, to a desired location.Subsequently nanowires 12 are further opened, thus releasing object 74in its appropriate location. In cases where object 74 fails to separatefrom nanowires 12, e.g., due to Van der Waals forces between object 74and nanowires 12, a further voltage can be applied between nanowires 12and the desired location, so that object 74 is released by anelectrostatic attractive force.

It is expected that during the life of this patent many relevantstructures of nanometric size will be developed and the scope of theterm nanostructure is intended to include all such new technologies apriori.

As used herein the term “about” refers to ±10%.

Additional objects, advantages and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the following examples, which are not intended to belimiting. Additionally, each of the various embodiments and aspects ofthe present invention as delineated hereinabove and as claimed in theclaims section below finds experimental support in the followingexamples.

EXAMPLES

Reference is now made to the following examples, which together with theabove descriptions, illustrate the invention in a non limiting fashion.

Generally, the nomenclature used herein and the laboratory proceduresutilized in the present invention include molecular, biochemical,microbiological and recombinant DNA techniques. Such techniques arethoroughly explained in the literature. See, for example, “MolecularCloning: A laboratory Manual” Sambrook et al., (1989); “CurrentProtocols in Molecular Biology” Volumes I-III Ausubel, R. M., ed.(1994); Ausubel et al., “Current Protocols in Molecular Biology”, JohnWiley and Sons, Baltimore, Md. (1989); Perbal, “A Practical Guide toMolecular Cloning”, John Wiley & Sons, New York (1988); Watson et al.,“Recombinant DNA”, Scientific American Books, New York; Birren et al.(eds) “Genome Analysis: A Laboratory Manual Series”, Vols. 1-4, ColdSpring Harbor Laboratory Press, New York (1998); methodologies as setforth in U.S. Pat. Nos. 4,666,828; 4,683,202; 4,801,531; 5,192,659 and5,272,057; “Cell Biology: A Laboratory Handbook”, Volumes I-III Cellis,J. E., ed. (1994); “Current Protocols in Immunology” Volumes I-IIIColigan J. E., ed. (1994); Stites et al. (eds), “Basic and ClinicalImmunology” (8th Edition), Appleton & Lange, Norwalk, Conn. (1994);Mishell and Shiigi (eds), “Selected Methods in Cellular Immunology”, W.H. Freeman and Co., New York (1980); available immunoassays areextensively described in the patent and scientific literature, see, forexample, U.S. Pat. Nos. 3,791,932; 3,839,153; 3,850,752; 3,850,578;3,853,987; 3,867,517; 3,879,262; 3,901,654; 3,935,074; 3,984,533;3,996,345; 4,034,074; 4,098,876; 4,879,219; 5,011,771 and 5,281,521;“Oligonucleotide Synthesis” Gait, M. J., ed. (1984); “Nucleic AcidHybridization” Hames, B. D., and Higgins S. J., eds. (1985);“Transcription and Translation” Hames, B. D., and Higgins S. J., Eds.(1984); “Animal Cell Culture” Freshney, R. I., ed. (1986); “ImmobilizedCells and Enzymes” IRL Press, (1986); “A Practical Guide to MolecularCloning” Perbal, B., (1984) and “Methods in Enzymology” Vol. 1-317,Academic Press; “PCR Protocols: A Guide To Methods And Applications”,Academic Press, San Diego, Calif. (1990); Marshak et al., “Strategiesfor Protein Purification and Characterization—A Laboratory CourseManual” CSHL Press (1996); all of which are incorporated by reference asif fully set forth herein. Other general references are providedthroughout this document. The procedures therein are believed to be wellknown in the art and are provided for the convenience of the reader. Allthe information contained therein is incorporated herein by reference.

Example 1 Self-Assembled Aromatic Peptides can be Used to Cast MetalNanowires Materials and Experimental Procedures

Material—Diphenylalanine peptides were purchases from Bachem (Bubendorf,Switzerland). Fresh stock solutions were prepared by dissolvinglyophilized form of the peptides in 1,1,1,3,3,3-Hexafluoro-2-propanol ata concentration of 100 mg/ml. To avoid any pre-aggregation, fresh stocksolutions were prepared for each and every experiment.

Transmission Electron microscopy—The peptides stock solutions werediluted to final concentration of 2 mg/ml in double distilled water.Then a 10 μl aliquot of 1 day-aged solution of peptide was placed on 200mesh copper grid, covered by carbon stabilized Formvar film. After 1minute, excess fluid was removed. For negative staining experiments, thegrid was stained with 2% uranyl acetate in water and after two minutesexcess fluid was removed from the grid. Silver-filled nanotubes wereimaged without staining. Samples were viewed using a JEOL 1200EXelectron microscope operating at 80 kV.

Digestion of the self-assembled structures by Proteinase K—Fresh stocksolutions of the L-Phe-L-Phe and D-Phe-D-Phe peptides were diluted to afinal concentration of 2 mg/ml. After one day, the peptide solutionswere examined for the presence of the self-assembled structures by TEMusing negative staining. The self-assembled structures were thenincubated with a solution of Proteinase K (20 μg/ml) for 1 hour at 37°C. and examined by TEM under the same experimental procedures.

Casting of metal nanowires—A 90 μl aliquot of nanotubes solution (agedfor one day) at a concentration of 2 mg/ml was added to a 10 μl boilingsolution of 10 mM AgNO₃. Citric acid was then added to reach a finalconcentration of 0.038% to serves as a reducing agent²⁰. Thesilver-filled nanotubes were then incubated with Proteinase K at a finalconcentration of 100 μg/ml for 1 hour at 37° C. Following the enzymaticdegradation, a 10 μl sample of the reaction solution was placed on TEMgreed and analyzed without staining.

Results

TEM analysis of diphenylalanine peptides showed a light shell and a darkcenter, as observed in FIG. 17, suggesting hollow tubular structuresfilled with the negative stain, uranyl acetate.

To study whether the tubes are truly hollow and filled with aqueoussolution, ionic silver was added to the nanotubes in solution.Energy-dispersive x-ray analysis (EDX) indicated the existence ofuranium within the assembled structures (FIG. 18 a). HR-TEMvisualization followed by EDX analysis indicated that silvernanoparticles were formed within the tubes (FIG. 18 b).

Based on these observations, the ability of the nanotubes to serve asmold for casting metal nanowires was addressed (FIG. 19 a). The tubeswere added to boiling ionic silver solution, and the silver was reducedwith citric acid to ensure a more uniform assembly of the silvernanowires [Henglein (1999) J. Phys. Chem. B. 103:9533; Enüstün (1963) J.Am. Chem. Soc. 85:3317]. TEM analysis in the absence of staining clearlyindicated the formation of metal assemblies within the majority (i.e.,80-90%) of the tubes (FIG. 19 b).

Proteolytic lysis of the peptide mold, by the addition of a Proteinase Kenzyme to the silver-filled nanotubes solution, resulted in theattainment of individual silver nanowires of about 20 nm in diameter asdetermined by TEM (FIGS. 2 c-d). The diameter of the nanowires, wassignificantly smaller than that of the tubes, further suggesting thatcasting was done inside the tubular structure. The chemical identity ofthe wire was confirmed by EDX analysis (FIG. 18 c).

Example 2

Tubular nanostructures were formed from naphthylalanine-naphthylalanine(Nal-Nal) dipeptides, in accordance with preferred embodiment of thepresent invention. The Chemical structure of the Nal-Nal dipeptide isschematically shown in FIG. 20.

Fresh stock solutions of Nal-Nal dipeptides were prepared by dissolvinglyophilized form of the peptides in 1,1,1,3,3,3-hexafluoro-2-propanol(HFIP, Sigma) at a concentration of 100 mg/mL. To avoid anypre-aggregation, fresh stock solutions were prepared for eachexperiment.

The peptides stock solutions were diluted into a final concentration of2 mg/mL in double distilled water, then the samples were placed on 200mesh copper grid, covered by carbon stabilized formvar film. Following 1minute, excess fluid was removed and the grid was negatively stainedwith 2% uranyl acetate in water. Following 2 minutes of staining, excessfluid was removed from the grid. Samples were viewed in JEOL 1200EXelectron microscope operating at 80 kV.

FIG. 21 is an electron microscope image of the samples, captured a fewminutes after the dilution of the peptide stock into the aqueoussolution. As shown, the dipeptides form thin (from several nanometers toa few tens of nanometers in diameter) and elongated (several microns inlength) tubular structures.

Example 3

Tubular and planar nanostructures were formed from by four differentdipeptides, in accordance with preferred embodiment of the presentinvention.

The following dipeptides were used:(Pentafluoro-Phenylalanine)-(Pentafluoro-Phenylalanine),(Iodo-Phenylalanine)-(Iodo-Phenylalanine), (4-Phenylphenylalanine)-(4-Phenyl phenylalanine) and(P-nitro-Phenylalanine)-(P-nitro-Phenylalanine).

For the first two dipeptides[(Pentafluoro-Phenylalanine)-(Pentafluoro-Phenylalanine) and(Iodo-Phenylalanine)-(Iodo-Phenylalanine)] fresh stock solutions wereprepared by dissolving lyophilized form of the peptides in DMSO at aconcentration of 100 mg/mL.

For the third and fourth dipeptides [(4-Phenyl phenylalanine)-(4-Phenylphenylalanine) and (P-nitro-Phenylalanine)-(P-nitro-Phenylalanine)],fresh stock solutions were prepared by dissolving lyophilized form ofthe peptides in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP, Sigma) at aconcentration of 100 mg/mL. To avoid any pre-aggregation, fresh stocksolutions were prepared for each experiment.

The peptides stock solutions were diluted into a final concentration of2 mg/mL in double distilled water.

In the case of (P-nitro-Phenylalanine)-(P-nitro-Phenylalanine) the finalconcentration was 5 mg/mL.

Subsequently, the samples were placed on 200 mesh copper grid, coveredby carbon stabilized formvar film. Following 1 minute, excess fluid wasremoved and the grid was negatively stained with 2% uranyl acetate inwater. Following 2 minutes of staining, excess fluid was removed fromthe grid. Samples were viewed in JEOL 1200EX electron microscopeoperating at 80 kV.

FIGS. 22A-D are electron microscope images of the four samples, captureda few minutes after the dilution of the peptide stock into the aqueoussolution.

FIG. 22A shows tubular assemblies formed by the(Pentafluoro-Phenylalanine)-(Pentafluoro-Phenylalanine) dipeptide, FIG.22B shows tubular structures assembled by(Iodo-Phenylalanine)-(Iodo-Phenylalanine), FIG. 22 C shows planarnanostructures formed by (4-Phenyl phenylalanine)-(4-Phenylphenylalanine), and FIG. 22D shows fibrilar assemblies of(P-nitro-Phenylalanine)-(P-nitro-Phenylalanine).

Altogether these results suggest the use of the peptide nanotubes of thepresent invention for numerous nano-technology applications.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

1. A method of encapsulating a metal in a tubular nanostructure, themethod comprising: (a) providing a discrete tubular nanostructurecomposed of a plurality of aromatic homodipeptides, the discrete tubularnanostructure having an internal cavity; and (b) introducing the metalinto said internal cavity of the discrete tubular nanostructure, therebyencapsulating the metal in the tubular nanostructure.
 2. A method ofencapsulating a metal in a tubular nanostructure, the method comprisingassembling a discrete tubular nanostructure composed of a plurality ofaromatic homodipeptides in the presence of the metal, therebyencapsulating the material in the nanostructure.
 3. The method of claim1, wherein said discrete tubular nanostructure does not exceed 500 nm indiameter.
 4. The method of claim 3, wherein said discrete tubularnanostructure is at least 1 nm in length.
 5. The method of claim 1,wherein said homodipeptides comprise a D-amino acid.
 6. The method ofclaim 1, wherein said homodipeptides comprise an L-amino acid.
 7. Themethod of claim 1, wherein said discrete tubular nanostructure is stableat a temperature range of 4-200° C.
 8. The method of claim 1, whereinsaid discrete tubular nanostructure is stable in an acidic environment.9. The method of claim 1, wherein the discrete tubular nanostructure isstable in a basic environment.
 10. The method of claim 1, wherein saidaromatic homodipeptides comprise Phe-Phe.
 11. The method of claim 1,wherein said aromatic homodipeptides are selected from the groupconsisting of naphthylalanine-naphthylalanine dipeptide,(pentafluoro-phenylalanine)-(pentafluoro-phenylalanine) dipeptide,(iodo-phenylalanine)-(iodo-phenylalanine) dipeptide, (4-phenylphenylalanine)-(4-phenyl phenylalanine) dipeptide and(p-nitro-phenylalanine)-(p-nitro-phenylalanine) dipeptide.
 12. Themethod of claim 1, wherein said metal is selected from the groupconsisting of silver, gold, copper, platinum, nickel and palladium. 13.The method of claim 1, wherein said discrete tubular nanostructure isobtained under non-saturation conditions which favor formation of thediscrete tubular nanostructure.
 14. The method of claim 13, wherein saidnon-saturation conditions comprise dissolving the peptides in1,1,1,3,3,3-hexafluoro-2-propanol at a concentration of 100 mg/ml andsubsequent dilution in water to a final concentration of 2 mg/ml.
 15. Amethod of positioning a target molecule at a predetermined location, themethod comprising: (a) providing a magnetic metal nanowire having atleast one segment associated with a functional group or ligand, saidfunctional group or ligand being capable of binding to the targetmolecule; (b) binding said magnetic metal nanowire to the targetmolecule; and (c) exposing said magnetic metal nanowire to a magneticfield, so as to position said magnetic metal nanowire and the targetmolecule at the predetermined location; wherein said magnetic metalnanowire is formed of a magnetic metal material at least partiallyenclosed by a nanostructure composed of a plurality of homodipeptides.16. The method of claim 15, wherein said magnetic material is aferromagnetic material.